The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index; none of the 26 sources its claims cite is checked for support yet.
Essential Role of Ubiquitin-Specific Protease 8 for Receptor Tyrosine Kinase Stability and Endocytic Trafficking In Vivo
Open accessAbstract
Posttranslational modification by ubiquitin controls multiple cellular functions and is counteracted by the activities of deubiquitinating enzymes. UBPy (USP8) is a growth-regulated ubiquitin isopeptidase that interacts with the HRS-STAM complex. Using Cre-loxP-mediated gene targeting in mice, we show that lack of UBPy results in embryonic lethality, whereas its conditional inactivation in adults causes fatal liver failure. The defect is accompanied by a strong reduction or absence of several growth factor receptor tyrosine kinases (RTKs), like epidermal growth factor receptor, hepatocyte growth factor receptor (c-met), and ERBB3. UBPy-deficient cells exhibit aberrantly enlarged early endosomes colocalizing with enhanced ubiquitination and have reduced levels of HRS and STAM2. Congruently immortalized cells gradually stop proliferation upon induced deletion of UBPy. These results unveil a central and nonredundant role of UBPy in growth regulation, endosomal sorting, and the control of RTKs in vivo.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
UBPy (USP8) is essential in vivo: constitutive deletion causes embryonic lethality, while induced deletion in adult mice causes fatal liver failure. UBPy maintains receptor tyrosine kinase protein levels and endocytic trafficking, at least in part by counteracting ubiquitination and stabilizing the HRS-STAM complex.
Key findings
- Heterozygote intercrosses yielded 13 UBPy+/+ (27.7%) and 34 UBPy+/− (72.3%) animals but no UBPy−/− mice; E9.5 mutant embryos were growth retarded and disorganized. Adult induced deletion caused death 4 to 6 days after poly(I:C), with severe liver failure, hyperbilirubinemia, and elevated liver enzymes.
- Immortalized UBPy-deficient MEFs stopped growing 6 to 8 days after tamoxifen-induced deletion, with severely reduced BrdU incorporation but no enhanced apoptosis/TUNEL in MEFs; in contrast, hepatocytes showed apoptosis.
- Loss of UBPy strongly reduced or eliminated RTKs: EGFR, c-met, and ERBB3 were decreased/absent in liver extracts, and EGFR was strongly reduced in cells; EGFR mRNA did not differ significantly, and EGF-induced Erk1/2 phosphorylation was impaired, while STAT1 phosphorylation was unaffected.
- UBPy-deficient cells showed enlarged EEA1-positive early endosomes, accumulated multivesicular bodies, reduced/absent HRS and STAM2, and enhanced ubiquitinated substrates colocalizing with enlarged endosomes; proteasomal activity was not impaired and free ubiquitin levels were unchanged, while ALIX and TSG101 were unaffected.
Methods
- Conditional Cre-loxP UBPy mice were generated by flanking exon IV with loxP sites; germline deletion used EIIa-Cre, and adult inducible deletion used MX-Cre with poly(I:C). Embryos were from heterozygous matings.
- Immortalized UBPy fl/fl MEFs expressing Cre-ERT2 were used for tamoxifen-inducible deletion; analyses included immunoblotting, Southern/Northern blotting, immunofluorescence, electron microscopy, BrdU incorporation, TUNEL, liver plasma analysis, and proteasome activity assays.
- EGF stimulation was performed after serum starvation with 100 ng/ml EGF; data are means ± standard errors of the mean, with statistical differences determined by Student’s t test.
Limitations
- The paper states that because of the severe liver phenotype and early death, cell-type-specific inactivation will be necessary to define the physiological relevance in other organs or cell types, and that detailed mechanisms leading to RTK reduction need to be defined.
- The paper notes that MX-Cre-mediated deletion is generally fastest and most efficient in the liver, which most likely explains why the phenotype manifests there although UBPy is also expressed in other cell types.
- Evident from the text: constitutive UBPy loss is embryonic lethal, limiting analysis of adult constitutive deletion; much mechanistic work relies on an immortalized MEF line and induced deletion, and the proposal that UBPy has two independent functions in RTK degradation is presented as a model.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 26 cited sources checked · 0 supported · 0 flagged
- Findingown data
UBPy-deficient fibroblasts underwent growth arrest.
“The observation that UBPy-deficient fibroblasts underwent growth arrest”
- Also stated in: § DISCUSSION · plain
“Impaired proliferation and growth arrest of immortalized cells upon deletion of UBPy.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
Lack of UBPy does not affect STAT-1 phosphorylation upon alpha/beta interferon induction.
“the lack of UBPy did not affect STAT-1 phosphorylation upon alpha/beta interferon induction”
Quote in the paperNot a substantial claim - Findingown data
Enhanced ubiquitination colocalized with enlarged early endosomes in UBPy-deficient cells.
“As shown in Fig. 7D, enhanced ubiquitination colocalized with the enlarged early endosomes”
Quote in the paperSubstantial claim - Findingown data
Histological analysis of liver sections revealed pathological changes starting 4 days after poly(I:C) administration, manifested by apoptotic hepatocytes around the central vein.
“Histological analysis of liver sections revealed that pathological changes started 4 days after the administration of poly(I ⅐ C), as manifested by apoptotic hepatocytes (Councilman bodies) around the central vein (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
ΔUBPy cells show accumulation of ubiquitinated substrates colocalizing with enlarged early endosomes.
“⌬UBPy cells show accumulation of ubiquitinated substrates colocalizing with enlarged early endosomes.”
Quote in the paperSubstantial claim
- Findingnone given
Loss of UBPy in hepatocytes caused apoptosis and cell death.
“As loss of UBPy in hepatocytes caused apoptosis and cell death”
Quote in the paperSubstantial claim - Findingnone given
UBPy-deficient animals are embryonic lethal.
“UBPy-deficient animals are embryonic lethal”
Quote in the paperSubstantial claim - Findingown data
Lack of UBPy causes accumulation of multivesicular bodies (MVBs).
“ultrastructural examination of ⌬UBPy cells by electron microscopy showed an accumulation of MVBs (Fig. 6B)”
Quote in the paperSubstantial claim - Findingown data
Induced inactivation of UBPy in adulthood causes fatal liver failure.
“induced inactivation in adulthood causes fatal liver failure.”
- Also stated in: § DISCUSSION · plain
“Deletion of UBPy in adult mice leads to death caused by disturbed liver function.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · plain
- Findingown data
Lack of UBPy causes endosomal enlargement.
“When UBPy-deficient cells were stained with the early endosomal marker EEA1, a drastic enlargement of early endosomes was detected (Fig. 6A).”
Quote in the paperSubstantial claim - Findingown data
Loss of UBPy is followed by a strong reduction of EGFR protein levels.
“the loss of UBPy was followed by a strong reduction of EGFR protein levels.”
Quote in the paperSubstantial claim - Findingown data
UBPy is not necessary to restore the pool of free ubiquitin.
“both types of cells showed the same amount of free ubiquitin, demonstrating that UBPy is not necessary to restore the pool of free ubiquitin”
Quote in the paperSubstantial claim - Findingown data
Proteasomal activity was even slightly higher in ΔUBPy liver extracts than in controls.
“As shown in Fig. 7B, even slightly higher proteasomal activity was detected in ⌬UBPy extracts”
Quote in the paperSubstantial claim - Findingown data
Strongly decreased HRS protein levels were detected in vivo in liver extracts of ΔUBPy mice.
“Strongly decreased HRS protein levels were also detected in vivo, as seen from the analysis of liver extracts of ⌬UBPy mice (Fig. 6D).”
Quote in the paperSubstantial claim - Findingown data
UBPy-deficient mice develop severe hyperbilirubinemia with dramatically increased concentrations of both conjugated and total bilirubin.
“the hyperbilirubinemia with dramatically increased concentrations of both conjugated and total bilirubin indicates severely disturbed liver function.”
Quote in the paperSubstantial claim - Findingown data
UBPy-deficient cells exhibit enlarged vacuole-like structures visible by light microscopy.
“exhibited enlarged vacuole-like structures already visible by light microscopy (see Fig. S3 in the supplemental material)”
Quote in the paperNot a substantial claim - Findingown data
Induced deletion of UBPy in an immortalized MEF cell line leads to growth arrest.
“cells completely stopped growing 6 to 8 days after deletion of UBPy.”
Quote in the paperSubstantial claim - Findingown data
EGFR mRNA levels did not differ significantly between UBPy+/+ and ΔUBPy animals.
“EGFR mRNA levels did not differ significantly between UBPy ϩ/ϩ and ⌬UBPy animals (Fig. 5D)”
Quote in the paperSubstantial claim - Findingown data
Absence of UBPy leads to a strong reduction or absence of HRS and STAM2 protein levels.
“The absence of UBPy led to a strong reduction, or even absence, of HRS and STAM2 protein levels”
Quote in the paperSubstantial claim - Findingown data
EGF signaling is impaired in UBPy-deficient cells, as appraised from phosphorylation of Erk1/2.
“EGF signaling was also impaired, as appraised from the phosphorylation of Erk1/2 (Fig. 5B).”
Quote in the paperSubstantial claim - Findingown data
Levels of ALIX and TSG101 were not affected by loss of UBPy.
“In contrast, levels of the UIM-containing proteins ALIX (36) and TSG101 (5,31), which are also associated with endosomal sorting processes, were not affected by the loss of UBPy (Fig. 6E and F).”
Quote in the paperSubstantial claim - Findingown data
Lack of UBPy results in embryonic lethality.
“no UBPy Ϫ/Ϫ mice, indicating that the lack of UBPy results in embryonic lethality.”
Quote in the paperSubstantial claim - Findingown data
UBPy-deficient cells exhibit enhanced ubiquitination.
“UBPydeficient cells exhibit aberrantly enlarged early endosomes colocalizing with enhanced ubiquitination and have reduced levels of HRS and STAM2.”
Quote in the paperSubstantial claim - Findingown data
BrdU incorporation in ΔUBPy cells was severely reduced.
“In concordance with impaired proliferation, BrdU incorporation in ⌬UBPy cells was severely reduced (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
Enhanced levels of ubiquitinated substrates were detected in liver extracts from ΔUBPy mice.
“Consistent with the function of UBPy as a DUB, enhanced levels of ubiquitinated substrates were detected in liver extracts from ⌬UBPy mice (Fig. 7A).”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy functions as a deubiquitinating enzyme (DUB).
- Findingown data
In UBPy-/- cells, endosomes can efficiently mature to MVBs even in the absence of the HRS-STAM complex.
“The observed accumulation of MVBs shows that in UBPy Ϫ/Ϫ cells, endosomes can efficiently mature to MVBs even in the absence of the HRS-STAM complex”
Quote in the paperSubstantial claim - Findingown data
Lack of UBPy causes progressive liver injury.
“Lack of UBPy causes progressive liver injury.”
Quote in the paperSubstantial claim - Findingown data
Induced inactivation of UBPy in MEF-derived cells correlates with decreased HRS and STAM2 protein levels.
“Induced inactivation of UBPy in the MEF-derived cell line correlates with decreased HRS and STAM2 protein levels.”
Quote in the paperSubstantial claim - Findingown data
Decreased protein levels of HRS and STAM2 were found in liver extracts from ΔUBPy mice.
“Decreased protein levels of HRS and STAM2 in liver extracts from ⌬UBPy mice.”
Quote in the paperSubstantial claim - Findingown data
In vivo UBPy is essential to maintain proper protein levels of RTKs, like EGFR, c-met, and ERBB3.
“We have shown that in vivo UBPy is essential to maintain proper protein levels of RTKs, like EGFR, c-met, and ERBB3”
- Also stated in: § DISCUSSION · boosted
“Lack of UBPy results in strongly reduced protein levels of the RTKs EGFR, ERBB3, and c-met.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · boosted
- Findingnone given
Embryonic fibroblasts did not exhibit enhanced apoptosis upon loss of UBPy.
“while embryonic fibroblasts did not exhibit enhanced apoptosis”
Quote in the paperNot a substantial claim - Findingown data
Absence of UBPy caused a severe reduction of HRS.
“As described here, the absence of UBPy caused a severe reduction of HRS.”
Quote in the paperSubstantial claim - Interpretationown data
UBPy has a functional role in endosomal sorting by stabilizing the HRS-STAM complex.
“These data provide strong evidence for a functional role of UBPy in endosomal sorting pursued by stabilizing the HRS-STAM complex.”
Quote in the paperSubstantial claim - Interpretationown data
Enhanced internalization followed by lysosomal degradation is the cause of the severe reduction of RTK protein levels in ΔUBPy mice.
“providing evidence that enhanced internalization followed by lysosomal degradation is the cause of the severe reduction of RTK protein levels (Fig. 5E).”
Quote in the paperSubstantial claim - Interpretationreasoning
Lack of UBPy cannot be compensated for by other DUB family members in vivo.
“This clearly shows that lack of UBPy cannot be compensated for by other DUB family members in vivo.”
Quote in the paperSubstantial claim - Interpretationcitation
The liver phenotype most likely manifests because MX-Cre-mediated deletion is fastest and most efficient in the liver.
“which most likely explains why the phenotype manifests in that organ”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy is expressed in other cell types.
- Premisecitation
HRS forms a complex with STAM2.
“In addition, HRS forms a complex with STAM2 (51), which was described as an interaction partner of UBPy (24).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] source
- Interpretationown data
The lack of EGFR protein expression in ΔUBPy livers is based on a disturbance of posttranscriptional regulation.
“demonstrating that the lack of EGFR protein expression is based on a disturbance of posttranscriptional regulation.”
Quote in the paperSubstantial claim - Interpretationreasoning
Embryonic lethality of UBPy-deficient animals might at least partially be attributed to the lack of HRS.
“Embryonic lethality might at least partially be attributed to the lack of HRS”
Quote in the paperSubstantial claim - Premisecitation
MX-Cre-mediated deletion of floxed genes in general leads to the fastest and most efficient deletion in the liver.
“MX-Cre-mediated deletion of floxed genes in general leads to the fastest and most efficient deletion in the liver (29)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] source
- Interpretationown data
UBPy has an essential, nonredundant function in vivo.
“demonstrating an essential, nonredundant function of UBPy in vivo (Fig. 2A).”
Quote in the paperSubstantial claim- Rests on an assumption: Poly(I:C) administration alone does not cause the lethal liver failure observed in ΔUBPy mice.
- Interpretationreasoning
Mouse models are necessary to evaluate functional properties of DUBs in vivo.
“underlining the necessity of mouse models to evaluate functional properties of DUBs in vivo.”
Quote in the paperNot a substantial claim - Interpretationown data
Proteasomal inhibition is not the cause of the enhanced ubiquitination levels in ΔUBPy extracts.
“suggesting that proteasomal inhibition is not the cause of the enhanced ubiquitination levels.”
Quote in the paperSubstantial claim - Interpretationown data
UBPy is essential for the stability of the HRS-STAM complex.
“indicating that UBPy is essential for the stability of the HRS-STAM complex.”
Quote in the paperSubstantial claim - Premisenone given
Bone marrow-derived macrophages from wt and CYLD-/- animals did not differ in innate immune receptor signaling.
“bone marrow-derived macrophages from wt and CYLD Ϫ/Ϫ animals did not differ in innate immune receptor signaling.”
Quote in the paperSubstantial claim - Interpretationown data
Lack of UBPy results in aberrant ubiquitination of substrates targeted to the endosomal-lysosomal degradation pathway.
“providing evidence that the lack of UBPy results in aberrant ubiquitination of substrates that are targeted to the endosomal lysosomal degradation pathway.”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy functions as a deubiquitinating enzyme (DUB).
- Interpretationreasoning
UBPy directly counteracts ubiquitination on distinct substrates.
“The results suggest that UBPy directly counteracts ubiquitination on distinct substrates.”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy functions as a deubiquitinating enzyme (DUB).
- Interpretationreasoning
The strong liver phenotype demonstrates that, besides a role in proliferation, UBPy is also essential in quiescent cells, like hepatocytes.
“The strong liver phenotype demonstrates that, besides a role in proliferation, UBPy is also essential in quiescent cells, like hepatocytes.”
Quote in the paperSubstantial claim - Premisecitation
HRS-deficient fibroblasts exhibit enlarged endosomes and enlarged vacuole-like structures, like UBPy-deficient MEFs.
“HRS-deficient fibroblasts also exhibit enlarged endosomes and show enlarged vacuole-like structures, like UBPy-deficient MEFs (27).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] source
- Interpretationown data
UBPy plays a critical role in cellular proliferation pursued via the control of RTK stability.
“The results show a critical role of UBPy in cellular proliferation pursued via the control of RTK stability.”
Quote in the paperSubstantial claim - Interpretationown data
UBPy has an essential role in the control of cellular proliferation.
“further supports an essential role of UBPy in the control of cellular proliferation.”
Quote in the paperSubstantial claim - Premisenone given
UBPy interacts with the HRS-STAM complex.
“UBPy (USP8) is a growth-regulated ubiquitin isopeptidase that interacts with the HRS-STAM complex.”
Quote in the paperSubstantial claim - Premisecitation
HRS-deficient animals exhibited embryonic lethality caused by ventral-folding defects.
“as HRS-deficient animals also exhibited embryonic lethality caused by ventral-folding defects.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] source
- Interpretationown data
UBPy does not exert a function similar to DOA4 in regeneration of free ubiquitin.
“does not exert a function similar to that of DOA4 in this respect.”
Quote in the paperSubstantial claim - Interpretationreasoning
Both activities might act in concert to regulate thresholds for RTK degradation.
“Both activities might act in concert to regulate thresholds for RTK degradation.”
Quote in the paperNot a substantial claim - Interpretationown data
Functional differences of UBPy in different cell types or in proliferating versus nonproliferating cells apparently exist.
“functional differences of UBPy in different cell types or in proliferating versus nonproliferating cells apparently exist.”
Quote in the paperNot a substantial claim - Premisecitation
HRS-/- drosophila pupae have reduced levels of EGFR.
“HRS Ϫ/Ϫ drosophila pupae have reduced levels of EGFR (34)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] source
- Interpretationcitation
The observed reduction of RTKs in UBPy-/- cells is unlikely to be caused by the lack of HRS but rather reflects a function of UBPy independent of the stabilization of the HRS-STAM complex.
“Thus, the observed reduction of RTKs in UBPy Ϫ/Ϫ cells is unlikely to be caused by the lack of HRS but rather reflects a function of UBPy independent of the stabilization of the HRS-STAM complex.”
Quote in the paperSubstantial claim - Interpretationcitation
Endosomal enlargement in UBPy-deficient cells most likely can be attributed to the lack of HRS.
“Endosomal enlargement in UBPy-deficient cells most likely can be attributed to the lack of HRS”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The observed cytoplasmic localization of EGFR in UBPy-deficient hepatocytes strongly suggests that, due to loss of UBPy, RTKs undergo enhanced internalization followed by lysosomal degradation.
“the observed cytoplasmic localization of EGFR in UBPy-deficient hepatocytes strongly suggests that, due to the loss of UBPy, RTKs undergo enhanced internalization followed by lysosomal degradation.”
Quote in the paperSubstantial claim - Interpretationreasoning
Reduced growth factor stimulation might at least partially contribute to the growth arrest in UBPy-/- cells.
“and thus reduced growth factor stimulation might at least partially contribute to the growth arrest in UBPy Ϫ/Ϫ cells.”
Quote in the paperSubstantial claim - Interpretationcitation
UBPy has an essential role in endocytic trafficking.
“supporting an essential role of UBPy in endocytic trafficking.”
Quote in the paperSubstantial claim - Premisecitation
Two reports described endosomal enlargement when UBPy was knocked down by RNA interference.
“While this work was in progress, two reports also described endosomal enlargement when UBPy was knocked down by RNA interference (7,48)”
Quote in the paperNot a substantial claim0 of 2 sources checked
- Probably not a substantial claim. 9
- The quote only partly states this claim. 1
- It may state two separate claims as one. 15
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. The quote only partly states this claim.
Findingown dataConditional inactivation of UBPy in adult mice causes fatal liver failure.
“Together, the data provide strong evidence that the death of ⌬UBPy mice is caused by a severe liver failure.”
Quote in the paperNot a substantial claim- Rests on an assumption: Poly(I:C) administration alone does not cause the lethal liver failure observed in ΔUBPy mice.
It may state two separate claims as one.
Findingown dataGrowth arrest in ΔUBPy MEFs was not accompanied by reduced cell viability or enhanced apoptosis.
“this was not accompanied by reduced cell viability or enhanced apoptosis, as cell numbers did not drop for a period of more than 10 days after growth arrest and the percentage of ⌬UBPy cells staining positive in a TUNEL assay was similar to that of undeleted cells”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataLiver injury in UBPy-deficient mice is confirmed by strongly increased serum concentrations of aspartate transaminase and alanine transaminase, accompanied by higher alkaline phosphatase and gamma-glutamyl-transferase, as well as glutaraldehyde dehydrogenase levels.
“Liver injury in mice lacking UBPy was further confirmed by strongly increased serum concentrations of aspartate transaminase and alanine transaminase and was accompanied by higher alkaline phosphatase and gamma-glutamyl-transferase, as well as glutaraldehyde dehydrogenase levels (Fig. 2B).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataUBPy-/- animals were extremely developmentally retarded and exhibited completely disorganized morphology at day 9.5.
“UBPy Ϫ/Ϫ animals were extremely developmentally retarded and exhibited completely disorganized morphology at that time point.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn liver extracts from ΔUBPy mice, c-met, EGFR, and ERBB3 protein levels were strongly decreased or below detection, whereas α-integrin and β-catenin levels were unchanged.
“c-met, EGFR, and ERBB3 protein levels in ⌬UBPy livers were strongly decreased (c-met) or even below detection levels (EGFR and ERBB3), whereas levels of ␣-integrin and -catenin were unchanged.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataLack of UBPy causes enlargement of early endosomes, accumulation of MVBs, and reduction of HRS and STAM2 in cells.
“Enlargement of early endosomes, accumulation of MVBs, and reduction of HRS and STAM2 in cells lacking UBPy.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationSTAM2 together with Hrs plays a regulatory role in endocytic trafficking of growth factor receptor complexes through early endosomes.
“STAM2 (Hbp), together with Hrs, plays a regulatory role in endocytic trafficking of growth factor receptor complexes through early endosomes (4).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] source
It may state two separate claims as one.
InterpretationreasoningBesides stabilization of HRS, UBPy is essential for embryonic growth.
“This shows that besides the stabilization of HRS, UBPy is essential for embryonic growth.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationCYLD has an essential role in T-cell development.
“Analysis of these mice instead demonstrated an essential role for CYLD in T-cell development (47)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] source
It may state two separate claims as one.
Interpretationown dataUBPy plays a central and nonredundant role in growth regulation, endosomal sorting, and the control of RTKs in vivo.
“These results unveil a central and nonredundant role of UBPy in growth regulation, endosomal sorting, and the control of RTKs in vivo.”
Quote in the paperSubstantial claim- Rests on an assumption: Poly(I:C) administration alone does not cause the lethal liver failure observed in ΔUBPy mice.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationUBPy protein levels decrease when cells undergo growth arrest by contact inhibition.
“Protein levels of UBPy decrease, when cells undergo growth arrest by contact inhibition, suggesting a possible role in the control of mammalian-cell proliferation (40).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationUBPy is a growth-regulated ubiquitin isopeptidase that accumulates upon growth stimulation.
“USP8 (UBPy/HUMORF8) was first described as a growthregulated ubiquitin isopeptidase that accumulates upon growth stimulation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] source
It may state two separate claims as one.
PremisecitationHRS-deficient embryos were often as large as wt controls and even had beating hearts by day 9.5.
“while HRS-deficient embryos were often as large as wt controls and even had beating hearts by day 9.5 (27)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] source
Probably not a substantial claim.
PremisecitationUpon ligand stimulation, RTKs undergo ubiquitin-mediated internalization leading to degradation via the endosomal-lysosomal pathway.
“It is well documented that upon ligand stimulation RTKs undergo ubiquitin-mediated internalization leading to degradation via the endosomal-lysosomal pathway (13,39).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim.
PremisecitationLigand binding induces ubiquitination as a signal to internalize the receptor via endocytosis for several RTKs.
“As a common feature of several RTKs, ligand binding induces ubiquitination as a signal to internalize the receptor via endocytosis (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationHRS binds directly to ubiquitinated proteins, which are then sorted to clathrin-coated microdomains while nonubiquitinated receptors, like transferrin or LDL receptor, are rapidly recycled to the cell surface.
“HRS binds directly to ubiquitinated proteins, which are then sorted to clathrin-coated microdomains while nonubiquitinated receptors, like transferrin or LDL receptor, are rapidly recycled to the cell surface (45).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] source
It may state two separate claims as one.
PremisecitationHRS-deficient murine cells and drosophila HRS-/- mutant larvae exhibit endosomal enlargement.
“as HRS-deficient murine cells and drosophila HRS Ϫ/Ϫ mutant larvae (27,34) were also reported to exhibit this phenotype.”
Quote in the paperSubstantial claim0 of 2 sources checkedIt may state two separate claims as one.
InterpretationreasoningUBPy exerts two independent functions in the RTK degradation pathway: directly counteracting RTK internalization and stabilizing the HRS-STAM complex.
“The results suggest that UBPy exerts two independent functions in the RTK degradation pathway, first by directly counteracting RTK internalization and second by stabilizing the HRS-STAM complex.”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy functions as a deubiquitinating enzyme (DUB).
It may state two separate claims as one.
InterpretationcitationPathology in the liver can most likely be attributed to the combined effects of disturbed endosomal function, loss of several RTKs, and disturbed liver regeneration caused by the absence of c-met.
“Pathology in the liver can most likely be attributed to the combined effects of disturbed endosomal function, loss of several RTKs, and disturbed liver regeneration caused by the absence of c-met”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationHRS is tyrosine phosphorylated upon stimulation with hepatocyte growth factor, platelet-derived growth factor, and epidermal growth factor.
“As HRS itself was identified as a protein that is tyrosine phosphorylated upon stimulation with hepatocyte growth factor, platelet-derived growth factor, and epidermal growth factor (26)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] source
It may state two separate claims as one.
PremisecitationUBPy directly interacts with EGFR resulting in EGFR deubiquitination.
“This is supported by results from Mizuno et al., who described a direct interaction of UBPy and the EGFR resulting in EGFR deubiquitination (38).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] source
It may state two separate claims as one.
InterpretationreasoningUBPy counteracts ubiquitination of RTKs or components of the endocytic machinery and thus regulates thresholds for the internalization of growth factor receptors.
“The results are compatible with a model in which UBPy counteracts ubiquitination of RTKs or components of the endocytic machinery and thus regulates thresholds for the internalization of growth factor receptors.”
Quote in the paperSubstantial claim- Rests on an assumption: UBPy functions as a deubiquitinating enzyme (DUB).
The paper relies on this without support.
Poly(I:C) administration alone does not cause the lethal liver failure observed in ΔUBPy mice.
“Mutant mice with the induced deletion of UBPy (⌬UBPy mice) died 4 to 6 days after the administration of poly(I ⅐ C)”
The paper relies on this without support.
UBPy functions as a deubiquitinating enzyme (DUB).
“Consistent with the function of UBPy as a DUB”
The paper relies on this without support.
UBPy is expressed in other cell types.
“although UBPy is also expressed in other cell types.”
The paper relies on this without support.
MVB maturation is a prerequisite of RTK degradation via the lysosomal pathway.
“a prerequisite of RTK degradation via the lysosomal pathway.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
USP8/UBPy has been previously implicated in the regulation of EGFR.
“The deubiquitinating enzyme ubiquitin-specific protease 8 (USP8/UBPy) has been previously implicated in the regulation of the epidermal growth factor receptor (EGFR); however, the molecular mechanisms governing its recruitment and activity in this context remain unclear.”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
USP8 is indispensable to cellular proliferation and survival.
“An essential growth-regulated enzyme, USP8, is indispensable to cellular proliferation and survival (23,24).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
Analysis of a conditional USP8 mouse knock-out revealed a drastic loss of growth factor receptors including EGFR, Erb-B3, and c-Met.
“Analysis of a conditional USP8 mouse knock-out has revealed a drastic loss of growth factor receptors, including the EGFR, its family member, Erb-B3, and c-Met (24).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
The current consensus in the literature indicates that USP8 functions to protect EGFR from ligand-induced down-regulation by direct deubiquitination of activated receptors.
“The current consensus in the literature indicates that USP8 functions to protect EGFR from ligand-induced down-regulation by virtue of direct deubiquitination of activated receptors (24,27,41).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
USP8 is required to deubiquitinate and protect EGFR from lysosomal degradation.
“USP8 is required to deubiquitinate and, thus, protect EGFR from lysosomal degradation (24,27,41).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
Our loss-of-function studies indicate a requirement for USP8 in EGFR stabilization and demonstrate that accelerated receptor degradation resulting from USP8 depletion proceeds through a pathway controlled by Hrs.
“In agreement with published evidence, our loss-of-function studies indicate a requirement for USP8 in EGFR stabilization (24,27,41) and demonstrate that accelerated receptor degradation, resulting from USP8 depletion, proceeds through a pathway controlled by Hrs (Fig. 1).”
From Regulation of Epidermal Growth Factor Receptor Ubiquitination and Trafficking by the USP8·STAM Complex (2010) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Mutant mice reported dead before day-7 sampling
MajorThe results state that mice with induced UBPy deletion died 4 to 6 days after poly(I 1⁄7 C) administration, but the Figure 2 caption says plasma was collected from 12 such mice seven days after induction.
“Mutant mice with the induced deletion of UBPy (⌬UBPy mice) died 4 to 6 days after the administration of poly(I ⅐ C), demonstrating an essential, nonredundant function of UBPy in vivo (Fig. 2A).”
“Seven days after poly(I ⅐ C) induction, plasmas of 10 UBPY ϩ/ϩ MX-Cre ϩ controls (open bars) and 12 UBPY fl/fl MX-Cre ϩ (⌬UBPy; solid bars) mice were analyzed.”
Citations
Cites
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,184
A genomic and functional inventory of deubiquitinating enzymes.
Nijman, S. M. B., Luna-Vargas, M. P. A., Velds, A., Brummelkamp, T. R., Dirac, A. M. G., Sixma, T. K., & Bernards, R. (2005) · Cell · doi:10.1016/j.cell.2005.11.007 · Cited by 1,854
Inducible Gene Targeting in Mice
Kühn, R., Schwenk, F., Aguet, M., & Rajewsky, K. (1995) · Science · doi:10.1126/science.7660125 · Cited by 1,641
Regulation of Membrane Protein Transport by Ubiquitin and Ubiquitin-Binding Proteins
Hicke, L., & Dunn, R. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.110701.154617 · Cited by 1,131
Efficient in vivo manipulation of mouse genomic sequences at the zygote stage.
Lakso, M., Pichel, J. G., Gorman, J. R., Sauer, B., Okamoto, Y., Lee, E., Alt, F. W., & Westphal, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.5860 · Cited by 1,125
Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization
Li, M., Chen, D., Shiloh, A., Luo, J., Nikolaev, A. Y., Qin, J., & Gu, W. J. (2002) · Nature · doi:10.1038/nature737 · Cited by 1,048
The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination
Kovalenko, A., Chable-Bessia, C., Cantarella, G., Israël, A., Wallach, D., & Courtois, G. (2003) · Nature · doi:10.1038/nature01802 · Cited by 1,018
Mechanism and function of deubiquitinating enzymes
Amerik, A. Y., & Hochstrasser, M. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.10.003 · Cited by 1,005
Regulation of Cre Recombinase Activity by Mutated Estrogen Receptor Ligand-Binding Domains
Feil, R., Wagner, J. D., METZGER, D., & Chambon, P. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7124 · Cited by 992
CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members
Trompouki, E., Hatzivassiliou, E., Tsichritzis, T., Farmer, H., Ashworth, A., & Mosialos, G. (2003) · Nature · doi:10.1038/nature01803 · Cited by 964
Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB
Brummelkamp, T. R., Nijman, S. M. B., Dirac, A. M. G., & Bernards, R. (2003) · Nature · doi:10.1038/nature01811 · Cited by 947
Ubiquitin and ubiquitin-like proteins as multifunctional signals
Welchman, R., Gordon, C., & Mayer, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1700 · Cited by 849
Huh, C.-G., Factor, V. M., Sánchez, A., Uchida, K., Conner, E. A., & Thorgeirsson, S. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306068101 · Cited by 750
Ubiquitylation and cell signaling
Haglund, K., & Đikić, I. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600808 · Cited by 736
Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation
Haglund, K., Sigismund, S., Polo, S., Szymkiewicz, I., Di Fiore, P. P., & Dikic, I. (2003) · Nature Cell Biology · doi:10.1038/ncb983 · Cited by 715
Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization
Matsuo, H., Chevallier, J., Mayran, N., Le Blanc, I., Ferguson, C., Fauré, J., Blanc, N. S., Matile, S., Dubochet, J., Sadoul, R., et al. (2004) · Science · doi:10.1126/science.1092425 · Cited by 705
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679
Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes
Raiborg, C., Bache, K. G., Gillooly, D. J., Madshus, I. H., Stang, E., & Stenmark, H. (2002) · Nature Cell Biology · doi:10.1038/ncb791 · Cited by 652
The Deubiquitinating Enzyme USP1 Regulates the Fanconi Anemia Pathway
Nijman, S. M. B., Huang, T. T., Dirac, A. M. G., Brummelkamp, T. R., Kerkhoven, R. M., D’Andrea, A. D., & Bernards, R. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.01.008 · Cited by 601
Regulation of monoubiquitinated PCNA by DUB autocleavage
Huang, T. T., Nijman, S. M. B., Mirchandani, K. D., Galardy, P. J., Cohn, M. A., Haas, W., Gygi, S. P., Ploegh, H. L., Bernards, R., & D’Andrea, A. D. (2006) · Nature Cell Biology · doi:10.1038/ncb1378 · Cited by 597
Met provides essential signals for liver regeneration
Borowiak, M., Garratt, A. N., Wüstefeld, T., Strehle, M., Trautwein, C., & Birchmeier, C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403412101 · Cited by 497
Hrs recruits clathrin to early endosomes
Raiborg, C., Bache, K. G., Mehlum, A., Stang, E., & Stenmark, H. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.5008 · Cited by 403
Hrs Regulates Endosome Membrane Invagination and Tyrosine Kinase Receptor Signaling in Drosophila
Lloyd, T. E., Atkinson, R., Wu, M. N., Zhou, Y., Pennetta, G., & Bellen, H. J. (2002) · Cell · doi:10.1016/s0092-8674(02)00611-6 · Cited by 401
The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer
Graner, E., Tang, D., Rossi, S., Baron, A., Migita, T., Weinstein, L. J., Lechpammer, M., Huesken, D., Zimmermann, J., Signoretti, S., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00055-8 · Cited by 368
Distinct monoubiquitin signals in receptor endocytosis
Haglund, K. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.09.005 · Cited by 367
Schumann, G., Bonora, R., Ceriotti, F., Férard, G., Ferrero, C. A., Franck, P., Gella, F.-J., Hoelzel, W., Jørgensen, P. J., Kanno, T., et al. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.124 · Cited by 362
Li, L.-M., & Cohen, S. N. (1996) · Cell · doi:10.1016/s0092-8674(00)81111-3 · Cited by 354
Williams, D., Tao, W., Yang, F., Kim, C., Gu, Y., Mansfield, P. J., Levine, J. E., Petryniak, B., Derrow, C. W., Harris, C., et al. (2000) · PubMed · Cited by 333
TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation
Lu, Q., Hope, L. W., Brasch, M., Reinhard, C., & Cohen, S. N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0932599100 · Cited by 301
Amerik, A. Y., Nowak, J. A., Swaminathan, S., & Hochstrasser, M. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.10.3365 · Cited by 298
Endocytosis of Receptor Tyrosine Kinases Is Driven by Monoubiquitylation, Not Polyubiquitylation
Mosesson, Y., Shtiegman, K., Katz, M., Zwang, Y., Vereb, G., Szollosi, J., & Yarden, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300096200 · Cited by 286
STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early Endosomes
Bache, K. G., Raiborg, C., Mehlum, A., & Stenmark, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210843200 · Cited by 286
Bishop, N. E., Horman, A., & Woodman, P. G. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200112080 · Cited by 266
Mizuno, E., Iura, T., Mukai, A., Yoshimori, T., Kitamura, N., & Komada, M. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-06-0560 · Cited by 248
Row, P. E., Prior, I. A., McCullough, J., Clague, M. J., & Urbé, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512615200 · Cited by 239
Osiak, A., Utermöhlen, O., Niendorf, S., Horak, I. D., & Knobeloch, K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6338-6345.2005 · Cited by 214
Self-citationKato, M., Miyazawa, K., & Kitamura, N. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007251200 · Cited by 213
Komada, M., & Soriano, P. (1999) · Genes & Development · doi:10.1101/gad.13.11.1475 · Cited by 209
Regulation of T cell development by the deubiquitinating enzyme CYLD
Reiley, W. W., Zhang, M., Jin, W., Losiewicz, M., Donohue, K. B., Norbury, C. C., & Sun, S.-C. (2006) · Nature Immunology · doi:10.1038/ni1315 · Cited by 198
Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
Amerik, A. Y., Li, S., & Hochstrasser, M. (2000) · Biological Chemistry · doi:10.1515/bc.2000.121 · Cited by 190
UBPY: a growth‐regulated human ubiquitin isopeptidase
Naviglio, S., Matteucci, C., Matoskova, B., Nagase, T., Nomura, N., Di Fiore, P. P., & Draetta, G. F. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3241 · Cited by 174
Two isoforms of otubain 1 regulate T cell anergy via GRAIL
Soares, L. R. B., Seroogy, C. M., Skrenta, H., Anandasabapathy, N., Lovelace, P. A., Chung, C. D., Engleman, E. G., & Fathman, C. G. (2003) · Nature Immunology · doi:10.1038/ni1017 · Cited by 167
Bowers, K., Piper, S. C., Edeling, M. A., Gray, S. R., Owen, D. J., Lehner, P. J., & Luzio, J. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508632200 · Cited by 166
Komada, M., & Kitamura, N. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.11.6213 · Cited by 149
Stabilization of the E3 Ubiquitin Ligase Nrdp1 by the Deubiquitinating Enzyme USP8
Wu, X., Yen, L., Irwin, L., Sweeney, C., & Carraway, K. L. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.17.7748-7757.2004 · Cited by 144
Schumann, G., Bonora, R., Ceriotti, F., Clerc-Renaud, P., Ferrero, C. A., Férard, G., Franck, P., Gella, F.-J., Hoelzel, W., Jørgensen, P. J., et al. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.110 · Cited by 139
Holzenberger, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.21.e92 · Cited by 129
Schumann, G., Bonora, R., Ceriotti, F., Férard, G., Ferrero, C. A., Franck, P., Gella, F.-J., Hoelzel, W., Jørgensen, P. J., Kanno, T., et al. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.125 · Cited by 111
Structural basis for SH3 domain‐mediated high‐affinity binding between Mona/Gads and SLP‐76
Harkiolaki, M., Lewitzky, M., Gilbert, R. J. C., Jones, E., Bourette, R. P., Mouchiroud, G., Sondermann, H., Moarefi, I., & Feller, S. M. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg258 · Cited by 102
Self-citationReexamination of the Role of Ubiquitin-Like Modifier ISG15 in the Phenotype of UBP43-Deficient Mice
Knobeloch, K., Utermöhlen, O., Kisser, A., Prinz, M., & Horak, I. D. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.11030-11034.2005 · Cited by 101
Self-citationGnesutta, N., Ceriani, M., Innocenti, M., Mauri, I., Zippel, R., Sturani, E., Borgonovo, B., Berruti, G., & Martegani, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103454200 · Cited by 98
Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes
Millard, S. M., & Wood, S. A. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200602082 · Cited by 71
Takata, H., Kato, M., Denda, K., & Kitamura, N. (2000) · Genes to Cells · doi:10.1046/j.1365-2443.2000.00303.x · Cited by 69
Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation
Kanazawa, C., Morita, E., Yamada, M., Ishii, N., Miura, S., Asao, H., Yoshimori, T., & Sugamura, K. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.08.078 · Cited by 68
Kaneko, T., Kumasaka, T., Ganbe, T., Sato, T., Miyazawa, K., Kitamura, N., & Tanaka, N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306677200 · Cited by 51
Janssen, J. W. G., Schleithoff, L., Bartram, C. R., & Schulz, A. (1998) · Oncogene · doi:10.1038/sj.onc.1201695 · Cited by 39
Flagged first, then by citations
Research works printed but not linked: 4
- Feil R., 1997, Naunyn-Schmiedebergs Arch. Pharmacol., 355, 41
- Huang T. T., 2006, Nat. Cell Biol., 8, 3309
- Schumann G., 2002, Clin. Chem. Lab. Med., 40, 725
- Williams D. A., 2000, Blood, 96, 1646
Cited by
Sorted by citations
Endocytosis and signalling: intertwining molecular networks
Sorkin, A., & von Zastrow, M. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2748 · Cited by 1,064
Deubiquitylating enzymes and drug discovery: emerging opportunities
Harrigan, J. A., Jacq, X., Martin, N. M., & Jackson, S. P. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.152 · Cited by 940
Endocytosis and intracellular trafficking of ErbBs
Sorkin, A. D., & Goh, L. K. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.07.029 · Cited by 776
Feedback regulation of EGFR signalling: decision making by early and delayed loops
Avraham, R., & Yarden, Y. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3048 · Cited by 690
Mutations in the deubiquitinase gene USP8 cause Cushing's disease
Reincke, M., Sbiera, S., Hayakawa, A., Theodoropoulou, M., Oßwald, A., Beuschlein, F., Meitinger, T., Mizuno-Yamasaki, E., Kawaguchi, K., Saeki, Y., et al. (2014) · Nature Genetics · doi:10.1038/ng.3166 · Cited by 611
Endocytosis of Receptor Tyrosine KinasesPreprint
Goh, L. K., & Sorkin, A. D. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a017459 · Cited by 478
Deubiquitinases in cancer: new functions and therapeutic options
Fraile, J. M., Quesada, V., Rodrı́guez, D., Freije, J. M. P., & López-Otı́n, C. (2011) · Oncogene · doi:10.1038/onc.2011.443 · Cited by 463
Deubiquitylases From Genes to Organism
Clague, M. J., Barsukov, I., Coulson, J. M., Liu, H., Rigden, D. J., & Urbé, S. (2013) · Physiological Reviews · doi:10.1152/physrev.00002.2013 · Cited by 438
Recurrent gain-of-function USP8 mutations in Cushing's disease
Ma, Z., Song, Z., Chen, J., Wang, Y., Li, S., Zhou, L., Mao, Y. Q., Li, Y., Hu, R., Zhang, Z., et al. (2015) · Cell Research · doi:10.1038/cr.2015.20 · Cited by 370
Endocytosis and signaling: Cell logistics shape the eukaryotic cell plan
Sigismund, S., Confalonieri, S., Ciliberto, A., Polo, S., Scita, G., & Di Fiore, P. P. (2012) · Physiological Reviews · doi:10.1152/physrev.00005.2011 · Cited by 338
A Strategy for Modulation of Enzymes in the Ubiquitin System
Ernst, A., Avvakumov, G. V., Tong, J., Fan, Y., Zhao, Y., Alberts, P., Persaud, A. K., Walker, J. R., Neculai, A.-M., Neculai, D., et al. (2013) · Science · doi:10.1126/science.1230161 · Cited by 289
Ubiquitination and the Regulation of Membrane Proteins
Foot, N. J., Henshall, T. L., & Kumar, S. (2016) · Physiological Reviews · doi:10.1152/physrev.00012.2016 · Cited by 271
Hussain, S., Zhang, Y., & Galardy, P. J. (2009) · Cell Cycle · doi:10.4161/cc.8.11.8739 · Cited by 261
The regulatory crosstalk between kinases and proteases in cancer
López-Otı́n, C., & Hunter, T. R. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2823 · Cited by 252
Mancini, A., Niemann‐Seyde, S. C., Pankow, R., Bounkari, O. E., Klebba-Färber, S., Koch, A., Jaworska, E., Spooncer, E., Gruber, A. D., Whetton, A. D., et al. (2010) · BMC Biology · doi:10.1186/1741-7007-8-1 · Cited by 241
Cellular functions of the DUBs
Clague, M. J., Coulson, J. M., & Urbé, S. (2012) · Journal of Cell Science · doi:10.1242/jcs.090985 · Cited by 233
Emerging roles of deubiquitinases in cancer‐associated pathways
Sacco, J. J., Coulson, J. M., Clague, M. J., & Urbé, S. (2010) · IUBMB Life · doi:10.1002/iub.300 · Cited by 200
When ubiquitination meets phosphorylation: a systems biology perspective of EGFR/MAPK signalling
Nguyen, L. K., Kölch, W., & Kholodenko, B. Ν. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-52 · Cited by 198
Regulation of proteolysis by human deubiquitinating enzymes
Eletr, Z. M., & Wilkinson, K. D. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.027 · Cited by 191
Protein partners of deubiquitinating enzymes
Ventii, K., & Wilkinson, K. D. (2008) · Biochemical Journal · doi:10.1042/bj20080798 · Cited by 186
Governance of Endocytic Trafficking and Signaling by Reversible Ubiquitylation
Clague, M. J., Liu, H., & Urbé, S. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.08.011 · Cited by 182
How Ubiquitin Functions with ESCRTs
Shields, S. B., & Piper, R. C. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01242.x · Cited by 180
Inactivation of HAUSP in vivo modulates p53 function.
Kon, N., Kobayashi, Y., Li, M., Brooks, C. L., Ludwig, T., & Gu, W. (2010) · Oncogene · doi:10.1038/onc.2009.427 · Cited by 176
The EGFR odyssey – from activation to destruction in space and time
Bakker, J., Spits, M., Neefjes, J., & Berlin, I. (2017) · Journal of Cell Science · doi:10.1242/jcs.209197 · Cited by 160
USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy
Xiong, W., Gao, X., Zhang, T., Jiang, B., Hu, M.-M., Bu, X., Gao, Y., Zhang, L., Xiao, B.-L., He, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29401-6 · Cited by 156
Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics
Antao, A. M., Tyagi, A., Kim, K.-S., & Ramakrishna, S. (2020) · Cancers · doi:10.3390/cancers12061579 · Cited by 153
Genome-wide Association Study Identifies Candidate Genes for Male Fertility Traits in Humans
Kosova, G., Scott, N. M., NIEDERBERGER, C. S., Prins, G. S., & Ober, C. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.04.016 · Cited by 149
USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy
Li, H., Sun, Y., Yao, Y., Ke, S., Zhang, N., Xiong, W., Shi, J., He, C., Xiao, X., Yu, H., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2315541121 · Cited by 143
Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt
Mukai, A., Yamamoto‐Hino, M., Awano, W., Watanabe, W., Komada, M., & Goto, S. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.100 · Cited by 137
Peng, H., Yang, F., Hu, Q., Sun, J., Peng, C., Zhao, Y., & Huang, C. (2020) · Autophagy · doi:10.1080/15548627.2019.1635381 · Cited by 116
Xia, R., Jia, H., Fan, J., Liu, Y., & Jia, J. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001238 · Cited by 131
Targeting ubiquitin specific proteases for drug discovery
Daviet, L., & Colland, F. (2008) · Biochimie · doi:10.1016/j.biochi.2007.09.013 · Cited by 126
Berlin, I., Schwartz, H., & Nash, P. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.016287 · Cited by 121
Berruti, G., & Paiardi, C. (2011) · Spermatogenesis · doi:10.4161/spmg.1.2.16820 · Cited by 117
Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis
von Zastrow, M., & Sorkin, A. D. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-081820-092427 · Cited by 115
Deubiquitylating Enzymes in Cancer and Immunity
Ren, J., Yu, P., Liu, S., Li, R., Niu, X., Chen, Y., Zhang, Z., Zhou, F., & Zhang, L. (2023) · Advanced Science · doi:10.1002/advs.202303807 · Cited by 107
Regulation of Endocytic Sorting by ESCRT–DUB-Mediated Deubiquitination
Wright, M. H., Berlin, I., & Nash, P. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9181-9 · Cited by 106
ErbB2 Trafficking and Degradation Associated with K48 and K63 Polyubiquitination
Marx, C., Held, J. M., Gibson, B. W., & Benz, C. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3768 · Cited by 102
Reverse the curse—the role of deubiquitination in cell cycle control
Song, L., & Rapé, M. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.01.012 · Cited by 101
Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes
Cruz, L. L., Soares, P., & Correia, M. (2021) · Pharmaceuticals · doi:10.3390/ph14090848 · Cited by 97
Edelmann, M. J., Nicholson, B., & Kessler, B. M. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002031 · Cited by 97
Chung, B. M., Raja, S. M., Clubb, R. J., Tu, C., George, M., Band, V., & Band, H. (2009) · BMC Cell Biology · doi:10.1186/1471-2121-10-84 · Cited by 89
The Multiple Layers of Ubiquitin-Dependent Cell Cycle Control
Wickliffe, K. E., Williamson, A. P., Jin, L., & Rapé, M. (2009) · Chemical Reviews · doi:10.1021/cr800414e · Cited by 91
Berlin, I., Higginbotham, K., Dise, R. S., Sierra, M. I., & Nash, P. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129411 · Cited by 90
Hasdemir, B., Murphy, J. E., Cottrell, G. S., & Bunnett, N. W. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025692 · Cited by 81
USP32 regulates late endosomal transport and recycling through deubiquitylation of Rab7
Sapmaz, A., Berlin, I., Bos, E., Wijdeven, R. H. M., Janssen, H., Konietzny, R., Akkermans, J. J. L. L., Erson-Bensan, A. E., Koning, R. I., Kessler, B. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09437-x · Cited by 84
Dufner, A., & Knobeloch, K. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190527 · Cited by 78
Self-citationDifferential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity
Walters, B. J., Campbell, S. L., Chen, P. C., Taylor, A. P., Schroeder, D. G., Dobrunz, L. E., Artavanis‐Tsakonas, K., Ploegh, H. L., Wilson, J. A., Cox, G. A., et al. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.07.028 · Cited by 78
Berruti, G., Ripolone, M., & Ceriani, M. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.109.081679 · Cited by 78
Development of inhibitors in the ubiquitination cascade
Zhang, W., & Sidhu, S. S. (2013) · FEBS Letters · doi:10.1016/j.febslet.2013.11.003 · Cited by 77
Tanaka, N., Kyuuma, M., & Sugamura, K. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00825.x · Cited by 76
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
Dufner, A., Kisser, A., Niendorf, S., Basters, A., Reißig, S., Schönle, A., Aichem, A., Kurz, T., Schlösser, A., Yablonski, D., et al. (2015) · Nature Immunology · doi:10.1038/ni.3230 · Cited by 75
Self-citationBedard, N., Yang, Y., Gregory, M., Cyr, D. G., Suzuki, J., Xiong, Y., Chian, R., Hermo, L., O’Flaherty, C., Smith, C. E., et al. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.110.088542 · Cited by 75
HIF1α deubiquitination by USP8 is essential for ciliogenesis in normoxia
Troilo, A., Alexander, I., Mühl, S., Jaramillo, D., Knobeloch, K., & Krek, W. (2013) · EMBO Reports · doi:10.1002/embr.201337688 · Cited by 75
Self-citationThe ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation
Liu, Z., Zanata, S. M., Kim, J., Peterson, M. A., Vizio, D. D., Chirieac, L. R., Pyne, S., Agostini, M., Freeman, M. R., & Loda, M. F. (2012) · Oncogene · doi:10.1038/onc.2012.188 · Cited by 74
Yeates, E. F. A., & Tesco, G. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.718023 · Cited by 70
Wei, R., Liu, X., Yu, W., Yang, T., Cai, W., Liu, J., Huang, X. S., Xu, G., Zhao, S., Yang, J., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3671 · Cited by 72
Critchley, W. R., Pellet‐Many, C., Ringham-Terry, B., Harrison, M. A., Zachary, I. C., & Ponnambalam, S. (2018) · Cells · doi:10.3390/cells7030022 · Cited by 71
Hui, A. Y., Meens, J., Schick, C., Organ, S. L., Qiao, H., Tremblay, E. A., Schäeffer, E., Uniyal, S., Chan, B. M. C., & Elliott, B. E. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22219 · Cited by 68
RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding
Wauman, J., Ceuninck, L. D., Vanderroost, N., Lievens, S., & Tavernier, J. H. (2011) · Journal of Cell Science · doi:10.1242/jcs.078055 · Cited by 67
Zhang, H., Han, B., Lu, H., Zhao, Y., Chen, X., Meng, Q., Cao, M., Cai, L., & Hu, J. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.07.002 · Cited by 66
Zhao, J., Bi, W., Zhang, J., Xiao, S., Zhou, R., Tsang, C. K., Lu, D., & Zhu, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.04.052 · Cited by 64
Shin, S., Kim, K., Kim, H.-R., Ylaya, K., Do, S.-I., Hewitt, S. M., Park, H.-S., Roe, J.-S., Chung, J.-Y., & Song, J. (2020) · Cell Death & Differentiation · doi:10.1038/s41418-019-0419-1 · Cited by 61
The ubiquitin system: orchestrating cellular signals in non-small-cell lung cancer
Fan, Q., Wang, Q., Cai, R., Yuan, H., & Xu, M. (2020) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-019-0193-6 · Cited by 58
USP8 suppresses death receptor-mediated apoptosis by enhancing FLIPL stability
Jeong, M., Lee, E.-W., Seong, D., Seo, J., Kim, J.-H., Grootjans, S., Kim, S.-Y., Vandenabeele, P., & Song, J. (2016) · Oncogene · doi:10.1038/onc.2016.215 · Cited by 58
ESCRT and Membrane Protein Ubiquitination
Migliano, S. M., & Teis, D. (2018) · Progress in molecular and subcellular biology · doi:10.1007/978-3-319-96704-2_4 · Cited by 58
Decoding the genetic basis of Cushing's disease: USP8 in the spotlight
Theodoropoulou, M., Reincke, M., Faßnacht, M., & Komada, M. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0320 · Cited by 57
Reciprocal cross-regulation between RNF41 and USP8 controls cytokine receptor sorting and processing
Ceuninck, L. D., Wauman, J., Masschaele, D., Peelman, F., & Tavernier, J. H. (2013) · Journal of Cell Science · doi:10.1242/jcs.131250 · Cited by 55
CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis
Crespo-Yàñez, X., Aguilar‐Gurrieri, C., Jacomin, A., Journet, A., Mortier, M., Taillebourg, E., Soleilhac, E., Weissenhorn, W., & Fauvarque, M. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007456 · Cited by 55
The role of deubiquitinating enzymes in spermatogenesis
Suresh, B., Lee, J., Hong, S., Kim, K.-S., & Ramakrishna, S. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2030-z · Cited by 54
Counts, S., He, B., Che, S., Ginsberg, S. D., & Mufson, E. J. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1196 · Cited by 54
Integration of cellular ubiquitin and membrane traffic systems: focus on deubiquitylases
Clague, M. J., & Urbé, S. (2017) · FEBS Journal · doi:10.1111/febs.14007 · Cited by 53
Role of Deubiquitinases in Human Cancers: Potential Targeted Therapy
Lai, K. P., Chen, J., & Tse, W. K. F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072548 · Cited by 52
The roles of ubiquitin modifying enzymes in neoplastic disease
Kumari, N., Jaynes, P. W., Saei, A., Iyengar, P. V., Richard, J. L. C., & Eichhorn, P. J. A. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.09.002 · Cited by 51
Neuroprotective Role for Galanin in Alzheimer’s Disease
Counts, S., Perez, S. E., Ginsberg, S. D., & Mufson, E. J. (2010) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0346-0228-0_11 · Cited by 50
Deubiquitylases in developmental ubiquitin signaling and congenital diseases
Basar, M. A., Beck, D. B., & Werner, A. A. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00697-5 · Cited by 48
Kim, Y., Shiba‐Ishii, A., Nakagawa, T., Iemura, S., Natsume, T., Nakano, N., Matsuoka, R., Sakashita, S., Lee, S., Kawaguchi, A., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0342-9 · Cited by 47
BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1
Ge, C., Che, L., Ren, J., PANDITA, R. K., Lu, J., Li, K., Pandita, T. K., & Du, C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418335112 · Cited by 45
Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?
Jacomin, A., Taillebourg, E., & Fauvarque, M. (2018) · Cells · doi:10.3390/cells7080112 · Cited by 44
CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in DrosophilaPreprint
Luo, W., Li, Y., Tang, C.-H. A., Abruzzi, K. C., Rodriguez, J., Pescatore, S., & Rosbash, M. (2012) · Genes & Development · doi:10.1101/gad.200584.112 · Cited by 42
The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43
Sun, J., Hu, Q., Peng, H., Peng, C., Zhou, L., Lu, J., & Huang, C. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001315 · Cited by 38
USP8 Controls the Trafficking and Sorting of Lysosomal Enzymes
MacDonald, E., Urbé, S., & Clague, M. J. (2014) · Traffic · doi:10.1111/tra.12180 · Cited by 37
Ubpy controls the stability of the ESCRT-0 subunit Hrs in development
Zhang, J., Du, J., Lei, C., Liu, M., & Zhu, A. J. (2014) · Development · doi:10.1242/dev.099564 · Cited by 37
Strategies for the identification of novel inhibitors of deubiquitinating enzymes
Goldenberg, S. J., McDermott, J. L., Butt, T. R., Mattern, M. R., & Nicholson, B. (2008) · Biochemical Society Transactions · doi:10.1042/bst0360828 · Cited by 37
USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels
Campbell, M. K., & Sheng, M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3305-17.2018 · Cited by 35
A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila
Jacomin, A.-C., Fauvarque, M.-O., & Taillebourg, E. (2016) · BMC Cell Biology · doi:10.1186/s12860-016-0115-7 · Cited by 36
Meccariello, R., Chianese, R., Ciaramella, V., Fasano, S., & Pierantoni, R. (2014) · BioMed Research International · doi:10.1155/2014/561426 · Cited by 34
Genetics of Cushing’s disease: an update
Perez‐Rivas, L. G., & Reincke, M. (2015) · Journal of Endocrinological Investigation · doi:10.1007/s40618-015-0353-0 · Cited by 33
An, W., Yao, S., Sun, X., Hou, Z., Lin, Y., Su, L., & Liu, X. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1182-3 · Cited by 33
Jeong, C. (2015) · Journal of Cancer Prevention · doi:10.15430/jcp.2015.20.1.57 · Cited by 33
Zhang, W., Zhang, Y., Zhang, H., Zhao, Q. C., Liu, Z., & Xu, Y. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27390 · Cited by 31
Jin, J., He, J., Li, X., Li, X., & Jin, X. (2023) · Gene · doi:10.1016/j.gene.2023.147807 · Cited by 31
USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET
Berruti, G., & Paiardi, C. (2015) · Reproduction · doi:10.1530/rep-14-0671 · Cited by 31
Jacomin, A.-C., Bescond, A., Soleilhac, E., Gallet, B., Schoehn, G., Fauvarque, M.-O., & Taillebourg, E. (2015) · PLOS ONE · doi:10.1371/journal.pone.0143078 · Cited by 30
Ubiquitination of the ubiquitin-binding machinery: how early ESCRT components are controlled
Korbei, B. (2022) · Essays in Biochemistry · doi:10.1042/ebc20210042 · Cited by 30
Roles for ER:endosome membrane contact sites in ligand-stimulated intraluminal vesicle formation
Wong, L. H., Eden, E. R., & Futter, C. E. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170432 · Cited by 29
Concise Review: Fate Determination of Stem Cells by Deubiquitinating Enzymes
Chandrasekaran, A. P., Suresh, B., Kim, S., Kim, K.-S., & Ramakrishna, S. (2016) · Stem Cells · doi:10.1002/stem.2446 · Cited by 27
Regulation of cellular responses by deubiquitinating enzymes: an update
James, F. B. (2011) · Frontiers in bioscience · doi:10.2741/3980 · Cited by 26
Cai, J., Crotty, T. M., Reichert, E. C., Carraway Kermit, L., Stafforini, D. M., & Topham, M. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.055731 · Cited by 26
Li, D., Feng, G., & He, L. (2009) · The World Journal of Biological Psychiatry · doi:10.1080/15622970903304442 · Cited by 25
Metadata
- Authors
- Niendorf, S., Oksche, A., Kisser, A., Löhler, J., Prinz, M., Schorle, H., Feller, S., Lewitzky, M., Horak, I., & Knobeloch, K.-P.
- Affiliations
- Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Leibniz Institute of Virology (LIV) (DE)
- University of Göttingen (DE)
- University of Bonn (DE)
- Cancer Research UK (GB)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-07-01
- Volume
- 27
- Issue
- 13
- Pages
- 5029-5039
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1951504
- OpenAlex
- W2069862324
- Semantic Scholar
- d85383238b90e64900ed63aa21883f499b7c3b68
- Cited by
- 207
- References
- 56
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 10 · 2018: 15 · 2017: 9 · 2016: 9 · 2015: 17 · 2014: 9 · 2013: 14 · 2012: 10
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- USP8, receptor tyrosine kinase, receptor stability, endosomal trafficking, STAM2, early endosomes, ubiquitination, epidermal growth factor receptor, c-Met, HER3, liver failure, embryonic lethality, growth regulation, cell proliferation
- MeSH terms
- Animals, Cell Line, Transformed, Death, Embryo, Mammalian, Endocytosis, Enzyme Stability, Fibroblasts, Humans, Liver, Endopeptidases, Endosomes, Mutagenesis, Gene Deletion, Gene Targeting, Proto-Oncogene Proteins c-met, Receptor Protein-Tyrosine Kinases, Receptor, ErbB-3, Ubiquitin, Ubiquitin Thiolesterase, Multiprotein Complexes, Cell Proliferation, Mice, Endosomal Sorting Complexes Required for Transport, ErbB Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
