CoChat
Sign Up
Cited by 24Ubiquitin and proteasome pathwaysCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index; 23 of the 45 sources its claims cite were checked for support.

SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1

Open access
Wang, Ju-Qiong, Lin, Zi-Cun, Li, Liang-Liang, Zhang, Shao-Fang, Li, Wei-Hui, Liu, Wei, Song, Bao-Liang, Luo, Jie·2021·Journal of Biological Chemistry
DOI 10.1074/jbc.ra120.015420PMC PMC7948399
Open this paper in CoChat — free account

Abstract

Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase mediating degradation of low-density lipoprotein (LDL) receptor (LDLR). IDOL also controls its own stability through autoubiquitination, primarily at lysine 293. Whether IDOL may undergo other forms of posttranslational modification is unknown. In this study, we show that IDOL can be modified by small ubiquitin-like modifier 1 at the K293 residue at least. The SUMOylation of IDOL counteracts its ubiquitination and augments IDOL protein levels. SUMOylation and the associated increase of IDOL protein are effectively reversed by SUMO-specific peptidase 1 (SENP1) in an activity-dependent manner. We further demonstrate that SENP1 affects LDLR protein levels by modulating IDOL. Overexpression of SENP1 increases LDLR protein levels and enhances LDL uptake in cultured cells. On the contrary, loss of SENP1 lowers LDLR levels in an IDOL-dependent manner and reduces LDL endocytosis. Collectively, our results reveal SUMOylation as a new regulatory posttranslational modification of IDOL and suggest that SENP1 positively regulates the LDLR pathway via deSUMOylation of IDOL and may therefore be exploited for the treatment of cardiovascular disease.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

IDOL is SUMOylated by SUMO1 primarily at K293, which competes with its autoubiquitination and stabilizes IDOL, thereby promoting LDLR degradation. SENP1 reverses IDOL SUMOylation, lowers IDOL abundance, and increases LDLR protein and LDL uptake in cultured cells.

Key findings

  • IDOL is conjugated with SUMO1, but not SUMO2 or SUMO3, mainly at K293; K293R significantly reduced SUMOylation, though it did not completely abolish it, suggesting additional sites.
  • SUMOylation elevates IDOL protein levels by inhibiting its autoubiquitination: co-expression of UBC9 plus SUMO1 increased IDOL, whereas K293R raised basal IDOL and made it resistant to further increase; ubiquitination of IDOL was greatly reduced when SUMOylation components were provided.
  • SENP1 deSUMOylates IDOL and reduces IDOL abundance in an activity-dependent manner; WT SENP1 dose-dependently reduced SUMO1-modified IDOL and IDOL protein, whereas catalytically inactive C603S SENP1 did not.
  • SENP1 increases LDLR and LDL uptake: SENP1 overexpression prevented IDOL-induced LDLR degradation, raised endogenous LDLR protein in stable CRL1601 cells without changing Ldlr/Idol mRNA, and accelerated DiI-LDL internalization; SENP1 knockdown or knockout lowered LDLR protein, and in SENP1 knockout cells internalized DiI-LDL was about half of control after a 1-h pulse.

Methods

  • Cultured cell systems: Huh7 human hepatocarcinoma cells, CRL1601 rat hepatoma cells, and HEK293T cells; CRISPR/Cas9 SENP1 and IDOL knockout lines and stable SENP1-Flag CRL1601 lines were generated.
  • Assays included Ni-NTA pull-down SUMOylation assays, anti-FLAG immunoprecipitation ubiquitination assays, immunoblotting, RT-qPCR, SUMO1-AMC and ubiquitin-AFC enzymatic assays, and DiI-LDL endocytosis imaging.
  • Data are presented as mean ± SEM and analyzed by unpaired two-tailed Student’s t test or one-way ANOVA, with significance set at p < 0.05.

Limitations

  • The paper states that the effect of SENP1 on plasma LDL-C in vivo could not be examined because IDOL is expressed at very low levels in mouse livers; it also notes that whether SUMOylation directly enhances IDOL ligase activity remains to be demonstrated.
  • The paper notes that SENP1 mRNA/protein is highly enriched in testis and that SENP1 polymorphisms have not yet been correlated with lipid-related diseases.
  • Evident from the text: most mechanistic work uses transfected/overexpressed proteins in cultured cells, and the authors note no commercial antibodies effectively detect endogenous IDOL, limiting endogenous IDOL analysis in some experiments.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1074/jbc.ra120.015420

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

23 of 45 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    IDOL is expressed at very low levels in mouse livers.

    “At the moment, we were not able to examine the effect of SENP1 on plasma LDL-C in vivo because IDOL is expressed at very low levels in mouse livers (8, 42).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source

      The supplied passage on transfected HEK293T cells says Idol protein levels are very low, even with expression from a vector. The mouse-tissue passages say LXR has only a modest effect on Idol expression in liver; they do not establish that baseline Idol levels in mouse liver are very low. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [42] Hong, 2014, The LXR-Idol axis differentially regulates plasma LDL levels in primates and mice, Cell Metab. source
  • Premisecitation

    IDOL is an E3 ubiquitin ligase.

    “As an E3 ubiquitin ligase, IDOL binds the cytoplasmic tail of LDLR via the N-terminal FERM 3b subdomain and triggers K48- and K63-linked polyubiquitination via the C-terminal really interesting new gene (RING) domain (6, 7, 8).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [6] Calkin, 2011, FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors, Proc. Natl. Acad. Sci. U. S. A. source
    • cites [7] Sorrentino, 2011, Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible degrader of the LDLR (IDOL), J. Biol. Chem. source
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source
  • Premisecitation

    IDOL is a critical regulator of the LDLR pathway.

    “Inducible degrader of the LDLR (IDOL, also known as myosin regulatory light-chain interacting protein) is another critical regulator of the LDLR pathway.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [6] Calkin, 2011, FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors, Proc. Natl. Acad. Sci. U. S. A. source
    • cites [7] Sorrentino, 2011, Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible degrader of the LDLR (IDOL), J. Biol. Chem. source
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source
  • Premisecitation

    IDOL mediates degradation of LDLR.

    “IDOL negatively modulates LDLR stability by targeting its degradation in lysosomes (6, 7, 8).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [6] Calkin, 2011, FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors, Proc. Natl. Acad. Sci. U. S. A. source
    • cites [7] Sorrentino, 2011, Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible degrader of the LDLR (IDOL), J. Biol. Chem. source
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source
  • Premisecitation

    IDOL deficiency facilitates LDLR-dependent clearance of ApoE and β-amyloid in the brain.

    “However, our findings are still of great importance considering that IDOL deficiency facilitates LDLR-dependent clearance of ApoE and β-amyloid in the brain, thereby reducing the formation and deposition of amyloid plaques and improving cognitive function in the mouse model of Alzheimer’s disease (46, 47).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [46] Choi, 2015, The E3 ubiquitin ligase idol controls brain LDL receptor expression, ApoE clearance, and Abeta amyloidosis, Sci. Transl. Med. source

      The Results section, “Loss of Idol facilitates ApoE and Aβ uptake and clearance” (page unavailable), reports increased uptake of both in Idol-deficient microglia and shows that LDLR knockdown largely abolished the increase in Aβ uptake. The paper also reports reduced amyloid plaque burden in APP/PS1 mice, but our copy does not report improved cognitive function, which the full citing sentence also attributes to the citations. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [47] Gao, 2020, Therapeutic IDOL reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice, Mol. Cell. Biol. source
  • Probably not a substantial claim. 16
  • It may state two separate claims as one. 13

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    PCSK9 is another potent LDLR degrader aside from IDOL.

    “PCSK9 is another potent LDLR degrader aside from IDOL (28, 29).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [28] Horton, 2009, PCSK9: a convertase that coordinates LDL catabolism, J. Lipid Res. source
    • cites [29] Lagace, 2014, PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells, Curr. Opin. Lipidol. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    VLDLR is another IDOL target protein.

    “Ablation of IDOL also prevents diet-induced obesity through controlling neuronal very low-density lipoprotein receptor (48), another IDOL target protein (49).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [49] Hong, 2010, The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2, J. Biol. Chem. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    SUMOylation promotes LRH-1 to interact with co-repressor Prox1, leading to reduced transcription of reverse cholesterol transport genes.

    “SUMOylation is also reported to promote the nuclear receptor liver receptor homolog 1 to interact with its co-repressor prosperso homeobox protein 1, leading to reduced transcription of the target genes involved in reverse cholesterol transport (25).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [25] Stein, 2014, SUMOylation-dependent LRH-1/PROX1 interaction promotes atherosclerosis by decreasing hepatic reverse cholesterol transport, Cell Metab. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    IDOL is a well-characterized transcriptional target of LXRs.

    “IDOL is a well-characterized transcriptional target of the liver X receptors (LXRs) (8, 32)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source
    • cites [32] Zhang, 2012, Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis, Arterioscler. Thromb. Vasc. Biol. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Polymorphisms in SENP1 have been correlated with chronic mountain sickness but not with lipid-related diseases as of yet.

    “Polymorphisms in SENP1 have been correlated with chronic mountain sickness (44, 45) but not with lipid-related diseases as of yet.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [44] Zhou, 2013, Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness in Andean highlanders, Am. J. Hum. Genet. source
    • cites [45] Azad, 2016, Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease, J. Exp. Med. source

  • It may state two separate claims as one.

    Premisecitation

    IDOL deficiency reduces the formation and deposition of amyloid plaques and improves cognitive function in the mouse model of Alzheimer's disease.

    “However, our findings are still of great importance considering that IDOL deficiency facilitates LDLR-dependent clearance of ApoE and β-amyloid in the brain, thereby reducing the formation and deposition of amyloid plaques and improving cognitive function in the mouse model of Alzheimer’s disease (46, 47).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [46] Choi, 2015, The E3 ubiquitin ligase idol controls brain LDL receptor expression, ApoE clearance, and Abeta amyloidosis, Sci. Transl. Med. source

      The Results section, “Loss of Idol decreases Aβ and reduces amyloid plaque burden,” reports reduced Aβ and plaque burden in APP/PS1 mice lacking Idol. The Results also link Idol deficiency to LDLR-dependent Aβ uptake, but do not establish improved cognitive function; the study design describes no cognitive assessment. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [47] Gao, 2020, Therapeutic IDOL reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice, Mol. Cell. Biol. source

  • It may state two separate claims as one.

    Premisecitation

    IDOL controls its own stability through autoubiquitination, primarily at lysine 293.

    “IDOL also controls its own stability through autoubiquitination, primarily at lysine 293.”
    • Also stated in: § SUMOylation elevates IDOL protein levels by inhibiting its autoubiquitination · plain
      “K293 residue, which is also the primary ubiquitination site (6)”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [6] Calkin, 2011, FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors, Proc. Natl. Acad. Sci. U. S. A. source
    • cites [8] Zelcer, 2009, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor, Science source

      The passage discussing Idol protein levels (section labeled Abstract; page unavailable) reports that a RING-domain mutation greatly increased Idol levels, raising the possibility that Idol catalyzes its own degradation. It does not establish autoubiquitination as the mechanism or identify lysine 293 as the primary site; the claim states the proposed mechanism as fact. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [11] Zhang, 2011, The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor, Genes Dev. source

      The section ‘Identification of the E2 for IDOL autoubiquitination’ reports IDOL autoubiquitination and says a RING-domain mutation abolishes IDOL’s ability to degrade itself. ‘IDOL is an iron-binding protein’ also links IDOL stability to autoubiquitination and degradation. Neither passage identifies lysine 293 as a primary autoubiquitination site; searches for ‘lysine 293’ and ‘K293R’ found no support for that detail. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    SENP1 mRNA and protein are present in many human tissues including the liver, and are highly enriched in the testis.

    “Further, SENP1 mRNA and protein, despite present in many human tissues including the liver, are highly enriched in the testis (43) (www.proteinatlas.org).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Xu, 2005, Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1, Biochem. J. source

      The ‘Distinct expression patterns’ section reports that SENP1 is highly expressed in testis and detectable in several other human tissues, including liver. However, the tissue-distribution experiment measured transcription by PCR, not SENP1 protein levels, so this source does not establish the claim about protein distribution. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    BRCA1, HERC2, and RNF168 are SUMOylated in response to genotoxic stress, which increases their ligase activity to support DNA damage repair.

    “For examples, BRCA1, HERC2, and RNF168 are SUMOylated in response to genotoxic stress for increased ligase activity so as to support DNA damage repair (36, 37).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [36] Morris, 2009, The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress, Nature source
    • cites [37] Danielsen, 2012, DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding zinc finger, J. Cell Biol. source

      The Results and discussion section (“SUMOylation of HERC2 and RNF168 in response to DSBs”; page not provided) reports increased SUMOylation of HERC2 and RNF168 after exposure to double-strand-break-inducing agents, but not other genotoxins. The Introduction links HERC2 SUMOylation to RNF8 binding and efficient ubiquitylation at damage sites. Our copy does not establish that BRCA1 is SUMOylated or that SUMOylation increases the ligase activity of all three proteins. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Ablation of IDOL prevents diet-induced obesity through controlling neuronal VLDLR.

    “Ablation of IDOL also prevents diet-induced obesity through controlling neuronal very low-density lipoprotein receptor (48), another IDOL target protein (49).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [48] Lee, 2019, IDOL regulates systemic energy balance through control of neuronal VLDLR expression, Nat. Metab. source

  • It may state two separate claims as one.

    Findingown data

    Silencing SENP1 decreases endogenous LDLR protein without affecting mRNA expression of LDLR or IDOL.

    “silencing of SENP1 decreased the endogenous LDLR protein level (Fig. 5A) without affecting the mRNA expression of LDLR or IDOL (Fig. 5B).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    GW3965 treatment induces transcription of LXR target genes including IDOL.

    “GW3965 treatment, albeit inducing the transcription of LXR target genes including IDOL (Fig. S2A)”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingcitation

    The K293R mutation largely, but not completely, abrogates both SUMOylation and ubiquitination of IDOL.

    “The K293R mutation largely, but not completely, abrogates both forms of modifications (Fig. 1) (6).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Calkin, 2011, FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors, Proc. Natl. Acad. Sci. U. S. A. source

  • It may state two separate claims as one.

    Findingown data

    SENP1 knockout profoundly reduces LDLR protein but not LDLR or IDOL mRNA.

    “we detected profoundly reduced expression of LDLR protein but not that of LDLR or IDOL mRNA (Fig. 5, E–F).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    SUMOylation enhances the ability of SMURF2 to degrade transforming growth factor β, a cytokine that normally promotes mammary epithelial morphogenesis.

    “SUMOylation also enhances the ability of SMURF2 to degrade transforming growth factor β, a cytokine that normally promotes mammary epithelial morphogenesis (38).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Chandhoke, 2016, The ubiquitin ligase Smurf2 suppresses TGFbeta-induced epithelial-mesenchymal transition in a sumoylation-regulated manner, Cell Death Differ. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    SUMOylation can regulate the activity of several E3 ubiquitin ligases.

    “SUMOylation can regulate the activity of several E3 ubiquitin ligases.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [36] Morris, 2009, The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress, Nature source
    • cites [37] Danielsen, 2012, DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding zinc finger, J. Cell Biol. source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [38] Chandhoke, 2016, The ubiquitin ligase Smurf2 suppresses TGFbeta-induced epithelial-mesenchymal transition in a sumoylation-regulated manner, Cell Death Differ. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    IDOL stabilization by USP2 decreases its ability to eliminate LDLR.

    “However, Nelson et al. (12) found that IDOL stabilization by USP2 decreased its ability to eliminate LDLR.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Nelson, 2016, The deubiquitylase USP2 regulates the LDLR pathway by counteracting the E3-ubiquitin ligase IDOL, Circ. Res. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    Nuclear SREBP2 can be SUMOylated at K464 for decreased transcriptional activity.

    “The nuclear form of sterol regulatory element-binding protein (SREBP) 2, the master transcriptional regulator of cholesterol biosynthesis and uptake, can be SUMOylated at the K464 residue for decreased transcriptional activity (24).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Hirano, 2003, Sterol regulatory element-binding proteins are negatively regulated through SUMO-1 modification independent of the ubiquitin/26 S proteasome pathway, J. Biol. Chem. source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    The SUMOylation-deSUMOylation cycle governs many biological processes by affecting protein stability, activity, localization, and interactions.

    “The SUMOylation–deSUMOylation cycle governs many biological processes by affecting protein stability, activity, localization as well as their interaction with other proteins (21).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Hendriks, 2016, A comprehensive compilation of SUMO proteomics, Nat. Rev. Mol. Cell Biol. source

  • It may state two separate claims as one.

    Interpretationreasoning

    SENP1-mediated deSUMOylation of IDOL increases LDLR expression and LDL endocytosis.

    “and, consequently, increases LDLR expression and LDL endocytosis”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    LXRs become SUMOylated in the presence of ligands, repressing inflammatory target genes.

    “LXRs as the oxysterol-sensitive nuclear receptors become SUMOylated in the presence of endogenous and/or synthetic ligands, thereby repressing the transcription of inflammatory target genes in multiple cell types (33, 34, 35).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [33] Lee, 2009, Differential SUMOylation of LXRalpha and LXRbeta mediates transrepression of STAT1 inflammatory signaling in IFN-gamma-stimulated brain astrocytes, Mol. Cell source
    • cites [34] Venteclef, 2010, GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response, Genes Dev. source

      Checked before — its earlier verdict is held back until a new check runs.

    • cites [35] Lee, 2016, Small heterodimer partner SHP mediates liver X receptor (LXR)-dependent suppression of inflammatory signaling by promoting LXR SUMOylation specifically in astrocytes, Sci. Signal. source

  • It may state two separate claims as one.

    Interpretationown data

    SENP1 increases LDLR protein and LDL uptake through deSUMOylating IDOL.

    “Altogether, these results demonstrate that SENP1 increases LDLR protein and LDL uptake through deSUMOylating IDOL.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Rsp5p, the only Nedd4-family HECT-type ubiquitin ligase in yeast, exhibits reduced activity upon SUMOylation, affecting ubiquitin-mediated endocytosis of the manganese transporter Smf1p.

    “By contrast, Rsp5p as the only member of the Nedd4 family of HECT-type ubiquitin ligases in yeast exhibits reduced activity upon SUMOylation, which eventually affects ubiquitin-mediated endocytosis of the manganese transporter Smf1p (39).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Novoselova, 2013, SUMOylation regulates the homologous to E6-AP carboxyl terminus (HECT) ubiquitin ligase Rsp5p, J. Biol. Chem. source

      Checked before — its earlier verdict is held back until a new check runs.

  • It may state two separate claims as one.

    Premisecitation

    The G51S mutation of IDOL increases IDOL protein stability and promotes IDOL-stimulated LDLR degradation.

    “In support of this statement, the G51S mutation of IDOL increases IDOL protein stability and promotes IDOL-stimulated LDLR degradation (13).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Adi, 2019, IDOL G51S variant is associated with high blood cholesterol and increases low-density lipoprotein receptor degradation, Arterioscler. Thromb. Vasc. Biol. source
24 of 24

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?

Citations

Cites

Flagged first, then by citations

1 of the 56 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Metadata

Authors
Wang, J.-Q., Lin, Z.-C., Li, L.-L., Zhang, S.-F., Li, W.-H., Liu, W., Song, B.-L., & Luo, J.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2021-01
Volume
296
Pages
100032
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.ra120.015420
PMC
PMC7948399
OpenAlex
W3096585176
Cited by
24
References
56
Citations by year
2026: 3 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 1
FWCI
0.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Ministry of Science and Technology of the People's Republic of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords
SUMOylation, SENP1, idols, E3 ubiquitin ligase, LDL receptor, LDL uptake, deSUMOylation, protein stability, post-translational modification, cardiovascular disease
MeSH terms
Cell Line, Cysteine Endopeptidases, Humans, Protein Processing, Post-Translational, Receptors, LDL, Ubiquitin-Protein Ligases, Ubiquitination, Sumoylation

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 2026-11-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

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