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POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation
Open accessAbstract
Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a nuclear form to modulate gene expression. To search for new genes regulating cholesterol metabolism, we perform a genome-wide CRISPR/Cas9 knockout screen and find that partner of site-1 protease (POST1), encoded by C12ORF49, is critically involved in the SREBP signaling. Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes. POST1 binds S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B’/B and C’/C. POST1 promotes the generation of the functional S1P-C’/C from S1P-B’/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well. This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase. Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
A genome-wide CRISPR/Cas9 screen identifies C12ORF49/POST1 as a regulator of cholesterol homeostasis that binds site-1 protease (S1P) and promotes its maturation. POST1 accelerates S1P-C′/C generation from S1P-B′/B and directly from S1P-A, thereby supporting SREBP processing and other S1P substrate cleavages.
Key findings
- In a GeCKO v2 screen of 65,383 sgRNAs targeting 19,050 human genes, 115 genes were highly enriched after five rounds of cholesterol depletion–repletion–amphotericin B selection, including NPC1, SCAP, LDLR, and C12ORF49/POST1; POST1 KO cells showed markedly improved resistance to amphotericin B even without U18666A.
- POST1 co-immunoprecipitated with S1P and promoted S1P-C′/C production at the expense of S1P-B′/B; it also supported S1P-C′/C generation from S1P-A via a non-canonical route, and co-expression of POST1 caused a greater than 5-fold increase in S1P localization to the Golgi.
- Loss of POST1 reduced cholesterol-depletion-induced nuclear SREBP2 and impaired induction of SREBP target genes including LSS, HMGCR, HMGCS1, SQLE, CYP51A1, FDFT1, SCD1, FASN, ACC1, INSIG1, and LDLR.
- POST1 deficiency also reduced cleavage of ATF6, CREB3L3, and the α/β-subunit precursor of GlcNAc-1-phosphotransferase, lowered M6P-modified proteins, increased α-mannosidase secretion, and caused enlarged lysosomes with cholesterol and LBPA accumulation.
Methods
- Genome-wide CRISPR/Cas9 knockout screen in HeLa/Cas9-Flag cells using the GeCKO v2 library at 0.3 MOI, followed by five rounds of cholesterol depletion–repletion–amphotericin B selection, deep sequencing of sgRNA inserts, and MAGeCK analysis.
- Mechanistic work used CRISPR/Cas9 POST1 and S1P KO HeLa lines, siRNA knockdown, RNA-seq, quantitative real-time PCR, immunoblotting, immunofluorescence, co-immunoprecipitation coupled to tandem mass spectrometry, membrane fractionation, and lysotracker/filipin staining.
- Data are presented as means ± SD and analyzed with GraphPad Prism 6; statistical significance was set at P < 0.05, with tests and sample sizes indicated in figure legends.
Limitations
- The paper states that the mechanism by which POST1 contributes to S1P-C′/C production is unknown, and that the physiological regulator of POST1 is worth investigating; it also notes that whether POST1 affects PCSK9 autoprocessing remains to be examined.
- Evident from the text: the findings rely heavily on HeLa cell lines, overexpression, knockout, and knockdown experiments, with no in vivo animal or human validation reported.
- Evident from the text: the initial screen phenotype is based on amphotericin B resistance as a proxy for plasma membrane cholesterol, and the study does not establish whether POST1 loss affects S1P maturation in physiological tissues.
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- Findingown data
The POST1-S1P interaction was confirmed by co-immunoprecipitation.
“The POST1–S1P interaction was confirmed by the co-immunoprecipitation assay (Fig. 4B).”
- Also stated in: § Abstract · plain
“POST1 binds S1P”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
The B'/B cleavage site mutant (BM, R130E/R134E) of S1P fails to yield S1P-B'/B and S1P-C'/C.
“The B’/B cleavage site mutant (BM, R130E/R134E) of S1P failed to yield S1P-B’/B and S1P-C’/C (lane 5)”
Quote in the paperSubstantial claim - Findingown data
S1P-B'/B is dramatically decreased when POST1 is co-expressed.
“S1P-B’/B was dramatically decreased when POST1 was co-expressed (compare lanes 5 and 6 of the 2nd blot)”
Quote in the paperSubstantial claim - Findingown data
25-hydroxycholesterol abrogates the upregulation of lipid metabolism-related genes caused by cholesterol depletion.
“25-HC as a potent inhibitor of the SREBP pathway abrogated the upregulation of lipid metabolism-related genes caused by cholesterol depletion.”
Quote in the paperNot a substantial claim - Findingown data
Among the 115 enriched genes were the known regulators NPC1, SCAP, and LDLR.
“among which included NPC1, SCAP and LDLR, the well-established regulators of cholesterol trafficking and metabolism.”
Quote in the paperNot a substantial claim
- Findingown data
No S1P autoprocessing is detected when the enzymatically inactive mutant (EM, D218A/H249A/S414A) is expressed alone or together with POST1.
“No S1P autoprocessing was detected when enzymatically inactive mutant (EM, D218A/H249A/S414A) was expressed alone (lane 3) or together with POST1 (lane 4)”
Quote in the paperSubstantial claim - Findingown data
POST1 has no effect on the autoprocessing of S1P with C'/C mutations.
“By contrast, POST1 had no effect on the autoprocessing of S1P with C’/C mutations (lane 8).”
Quote in the paperSubstantial claim - Findingown data
Three independent POST1 knockout cell lines show markedly reduced n-SREBP2 compared with wild-type controls.
“We generated three independent lines of POST1 KO cells and found markedly reduced n-SREBP2 compared with WT controls (Fig. 3F and S1B).”
Quote in the paperSubstantial claim - Findingown data
POST1 knockout cells in ample cholesterol show SREBP2 predominantly localized in the ER.
“SREBP2 was predominately localized in the ER in the presence of ample cholesterol (Fig. 3B, top row)”
Quote in the paperSubstantial claim - Findingown data
25-HC decreases both Golgi and nuclear SREBP2 staining in POST1 knockout cells to levels seen in FBS-treated cells.
“25-HC decreased both Golgi and nuclear SREBP2 staining to the levels seen in FBS-treated cells (Fig. 3B, bottom row; Fig. 3C and 3D).”
Quote in the paperSubstantial claim - Findingown data
POST1 increases S1P-C'/C formation when co-expressed with S1P-Flag, HA-1, or HA-2.
“The anti-Flag blot (Fig. 4F, the 1st blot) showed that POST1 increased S1P-C’/C formation when co-expressed with S1P-Flag, HA-1 or HA-2.”
Quote in the paperSubstantial claim - Findingown data
Wild-type cells deprived of cholesterol show robust nuclear SREBP2 staining.
“those deprived of cholesterol had robust staining in the nucleus (Fig. 3A, middle row; Fig. 3C)”
Quote in the paperSubstantial claim - Findingown data
n-SREBP2 is evident in wild-type cells depleted of cholesterol but barely detectable in POST1 knockout cells.
“n-SREBP2 was evident in WT cells depleted of cholesterol but barely detectible in POST1 KO cells (Fig. 3E).”
- Also stated in: § Abstract · plain
“Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
Wild-type cells cultured in 10% FBS show an ER distribution of SREBP2.
“WT cells cultured in 10% FBS showed an ER distribution of SREBP2 (Fig. 3A, top row; Fig. 3C and 3D)”
Quote in the paperNot a substantial claim - Findingown data
The cholesterol-starvation-induced increase in SREBP target gene expression is much more moderate in POST1 knockout cells than in wild-type cells.
“However, these increases were much moderate when POST1 was ablated.”
- Also stated in: § Abstract · plain
“Ablation of POST1 decreases the generation of nuclear SREBP and reduces the expression of SREBP target genes.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
Wild-type cells exposed to 25-HC show SREBP2 mainly in the ER.
“SREBP2 was mainly found in the ER of WT cells exposed to 25-HC (Fig. 3A, bottom row).”
Quote in the paperNot a substantial claim - Findingown data
In both wild-type and POST1 knockout cells, expression of SREBP2 target genes (cholesterol metabolism) and SREBP1c target genes (fatty acid metabolism) is markedly elevated upon cholesterol starvation.
“In both WT and POST1 KO cells, the expression of SREBP2 target genes (cholesterol metabolism) and SREBP1c target genes (fatty acid metabolism) was markedly elevated upon cholesterol starvation (Fig. 2A; Table S2).”
Quote in the paperSubstantial claim - Findingown data
Upon POST1 co-expression, a band corresponding to prodomain (I+II) appears in cells expressing HA-1 or HA-2.
“Upon POST1 co-expression, a band corresponding to the prodomain (I+II) appeared in the cells expressing HA-1 or HA-2 (lanes 4 and 6 of the 3rd blot).”
Quote in the paperSubstantial claim - Findingown data
In cells lacking endogenous POST1, POST1 promotes S1P-C'/C generation at the expense of S1P-B'/B.
“As in the WT cells, POST1 promoted S1P-C’/C generation at the expense of S1P-B’/B as well (Fig. 4E, compare lanes 1 and 2).”
Quote in the paperSubstantial claim - Findingown data
MS/MS analysis of POST1-interacting proteins from three independent experiments identified S1P among highly enriched proteins.
“Analysis of the MS/MS results from three independent experiments revealed a set of highly enriched proteins including S1P (encoded by MBTPS1) (Fig. 4A; Table S3).”
Quote in the paperSubstantial claim - Findingown data
A genome-wide CRISPR/Cas9 knockout screen identified 115 genes highly enriched in cells that survived five rounds of amphotericin B challenge.
“A total of 115 genes were found highly enriched in the cells survived 5 rounds of challenge (Fig. 1B; Table S1)”
Quote in the paperSubstantial claim - Findingown data
POST1 knockout HeLa cells show markedly improved resistance to amphotericin B compared with wild-type cells even in the absence of U18666A.
“POST1 KO cells showed markedly improved resistance to AmB even in the absence of U18666A (Fig. 1C).”
Quote in the paperSubstantial claim - Findingown data
POST1 knockout cells upon cholesterol depletion show SREBP2 redistributed to the Golgi complex with slight nuclear staining.
“redistributed to the Golgi complex with slight staining in the nucleus upon cholesterol depletion (Fig. 3B, middle row; Fig. 3C and 3D)”
Quote in the paperSubstantial claim - Findingown data
The uncharacterized gene C12ORF49 was robustly enriched in the screen.
“we also detected robust enrichment of an uncharacterized gene C12ORF49”
Quote in the paperSubstantial claim - Findingown data
siRNA knockdown of POST1 hampers cholesterol depletion-induced SREBP2 cleavage to a similar extent as knockdown of SCAP.
“knockdown of POST1 using small interfering RNA (siRNA) hampered cholesterol depletion-induced SREBP2 cleavage to a similar extent as knockdown of SCAP (Fig. 3G and S1C).”
Quote in the paperSubstantial claim - Findingown data
Intracellular abundance of α-mannosidase is significantly decreased in POST1-deficient cells.
“The intracellular abundance of α-mannosidase, an M6P-modified lysosomal enzyme, was significantly decreased but its secretion to the medium was greatly increased (Fig. 6E).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
S1P is mainly retained in the ER when co-expressed with POST1-EGFP-KDEL.
“S1P was mainly retained in the ER when co-expressed with POST1-EGFP-KDEL (Fig. 5F and 5G).”
Quote in the paperSubstantial claim - Findingown data
POST1-EGFP-KDEL facilitates the production of S1P-C'/C.
“We demonstrate that POST1-EGFP-KDEL facilitates the production of S1P-C’/C, and that the S1P mutants that cannot be converted to the active form are mainly present in the ER (Fig. 5C and 5G).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Deficiency of POST1 largely inhibits cleavage of the α/β-subunit precursor of GlcNAc-1-phosphotransferase to release α and β subunits.
“As shown in Fig. 6C, deficiency of POST1 largely inhibited the cleavage of the α/β-subunit precursor to release α and β subunits.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
POST1-mediated S1P activation is essential for the cleavages of other S1P substrates including ATF6, CREB3 family members, and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase.
“This POST1-mediated S1P activation is also essential for the cleavages of other S1P substrates including ATF6, CREB3 family members and the α/β-subunit precursor of N-acetylglucosamine-1-phosphotransferase.”
Quote in the paperSubstantial claim - Findingown data
Loss of C12ORF49/POST1 attenuated SREBP target gene expression.
“Our screen uncovered C12ORF49/POST1, the loss of which increased AmB resistance (Fig. 1C), attenuated SREBP target gene expression (Fig. 2A and 2B) and blocked SREBP processing (Fig. 3).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
The genome-scale CRISPR/Cas9 KO screen coupled to the cholesterol depletion-repletion-AmB selection challenge enriched genes involved in LDL uptake and cholesterol trafficking to the PM.
“For this purpose, we performed a genome-scale, unbiased CRISPR/Cas9 KO screen coupled to the “cholesterol depletion-repletion-AmB selection” challenge (Fig. 1A), so that genes involved in LDL uptake and cholesterol trafficking to the PM were highly enriched.”
Quote in the paperSubstantial claim- Rests on an assumption: The AmB selection challenge enriches for genes involved in LDL uptake and cholesterol trafficking to the PM.
- Findingown data
Co-expression of POST1 causes a greater than 5-fold increase in S1P localization to the Golgi complex.
“Co-expression of POST1 caused a greater than 5-fold increase in S1P localization to the Golgi complex (Fig. 5A and 5B).”
Quote in the paperSubstantial claim - Findingown data
The process of S1P-C'/C production is abolished by the D218A/H249A/S414A mutations.
“However, this process is abolished by the D218A/H249A/S414A mutations (Fig. 4E), suggesting an absolute dependency on S1P enzymatic activity.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
POST1-deficient cells have enlarged lysosomes.
“POST1-deficient cells had enlarged lysosomes as revealed by the LAMP1 and lysotracker staining (Fig. 6F).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Secretion of α-mannosidase to the medium is greatly increased in POST1-deficient cells.
“The intracellular abundance of α-mannosidase, an M6P-modified lysosomal enzyme, was significantly decreased but its secretion to the medium was greatly increased (Fig. 6E).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingreasoning
Less SCAP is detected in POST1-KO cells under the sterol-depletion condition.
“As cholesterol depletion promotes ER-to-Golgi transport of SCAP and SCAP is degraded when SREBP cannot be efficiently cut by S1P, less SCAP was detected in POST1-KO cells under the sterol-depletion condition (Fig. S3A).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
S1P mutants that cannot be converted to the active form are mainly present in the ER.
“We demonstrate that POST1-EGFP-KDEL facilitates the production of S1P-C’/C, and that the S1P mutants that cannot be converted to the active form are mainly present in the ER (Fig. 5C and 5G).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Mutations in enzymatic activity (EM) and B'/B or C'/C cleavage sites (BM and CM) severely impair POST1-induced translocation of S1P from the ER to the Golgi.
“Notably, mutations in enzymatic activity (EM) and B’/B or C’/C cleavage sites (BM and CM) severely impaired POST1-induced translocation of S1P from the ER to the Golgi (Fig. 5C and 5D).”
Quote in the paperSubstantial claim - Findingown data
Loss of C12ORF49/POST1 blocked SREBP processing.
“Our screen uncovered C12ORF49/POST1, the loss of which increased AmB resistance (Fig. 1C), attenuated SREBP target gene expression (Fig. 2A and 2B) and blocked SREBP processing (Fig. 3).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Loss of C12ORF49/POST1 increased AmB resistance.
“Our screen uncovered C12ORF49/POST1, the loss of which increased AmB resistance (Fig. 1C), attenuated SREBP target gene expression (Fig. 2A and 2B) and blocked SREBP processing (Fig. 3).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Both KDEL- and KDAS-tagged POST1-EGFP facilitate S1P-C'/C production as the wild-type version does.
“both KDEL- or KDAS-tagged POST1-EGFP could facilitate S1P-C’/C production as the WT version did (Fig. 5E).”
Quote in the paperSubstantial claim - Findingown data
Overall levels of M6P-modified proteins are reduced in cells lacking POST1 or S1P.
“In line with this, the overall levels of M6P-modified proteins were reduced in cells lacking POST1 or S1P (Fig. 6D).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Depletion of POST1 or S1P similarly reduces SCAP level.
“Consistently, depletion of POST1 or S1P similarly reduced SCAP level (Fig. S3A and S3B).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
POST1 KO cells had less amounts of the cleaved nuclear form of ATF6 (n-ATF6) and CREB3L3 (n-CREB3L3) than WT cells exposed to thapsigargin for various periods.
“POST1 KO cells had less amounts of the cleaved nuclear form of ATF6 (n-ATF6) and CREB3L3 (n-CREB3L3) than WT cells, suggestive of impaired cleavage of ATF6 and CREB3L3 in the absence of POST1.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Findingown data
Co-expression of S1P and POST1 dramatically promotes the nuclear localization of SREBP2.
“Co-expression of S1P and POST1 dramatically promoted the nuclear localization of SREBP2 (Fig. S2A; Movie S1).”
Quote in the paperSubstantial claim - Interpretationown data
POST1 promotes S1P-A cleavage at the C'/C sites.
“These results support the notion that POST1 promotes S1P-A cleavage at the C’/C sites.”
Quote in the paperSubstantial claim - Premisecitation
S1P is synthesized as an inactive precursor and undergoes multiple processing of its N-terminal prodomain involving the catalytic triad D218/H249/S414, generating S1P-A, S1P-B'/B, and S1P-C'/C.
“S1P is synthesized as an inactive precursor whose domain organization is shown in Fig. 4C. To become mature, S1P undergoes multiple processing of the N-terminal prodomain involving the catalytic triad D218/H249/S414, generating three shortened forms designated S1P-A, S1P-B’/B and S1P-C’/C (Espenshade et al., 1999; Elagoz et al., 2002; da Palma et al., 2014).”
- Also stated in: § Abstract · plain
“S1P, which is synthesized as an inactive protease (form A) and becomes fully mature via a two-step autocatalytic process involving forms B’/B and C’/C.”
Quote in the paperSubstantial claim0 of 3 sources checked - Also stated in: § Abstract · plain
- Interpretationown data
POST1 has a positive role in regulating plasma membrane cholesterol level.
“Overall, these results support a positive role of POST1 in regulating PM cholesterol level.”
Quote in the paperSubstantial claim - Interpretationown data
POST1 is a key regulator of SREBP processing.
“Together, these results establish POST1 as a key regulator of SREBP processing.”
Quote in the paperSubstantial claim - Interpretationown data
POST1 promotes S1P-B'/B cleavage at the C'/C sites.
“indicating POST1 also promotes S1P-B’/B cleavage at the C’/C sites.”
Quote in the paperSubstantial claim - Interpretationcitation
S1P cleavage at the B'/B sites is required for subsequent cleavage at the C'/C sites.
“These results are consistent with the earlier work (Espenshade et al., 1999; da Palma et al., 2014), and suggest that S1P cleavage at the B’/B sites is required for subsequent cleavage at the C’/C sites.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
S1P enzymatic activity is a prerequisite for its self-cleavage regardless of the presence of POST1.
“suggesting that S1P enzymatic activity is a prerequisite for its self-cleavage regardless of the presence of POST1.”
Quote in the paperSubstantial claim - Interpretationown data
POST1 may aid S1P autoprocessing bypassing the B'/B sites.
“However, we observed S1P-C’/C, albeit in small amounts, in S1P-KO cells co-transfected with S1P B’/B mutant and POST1 (lane 6), suggesting that POST1 may aid S1P autoprocessing bypassing the B’/B sites.”
Quote in the paperSubstantial claim - Interpretationown data
POST1 resides in both the ER and Golgi.
“These results suggest that POST1 resides in both the ER and Golgi.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Through modulating S1P maturation, POST1 is critically involved in the processing of SREBP, ATF6, CREB3 family members and other S1P substrates.
“Through modulating S1P maturation, POST1 is critically involved in the processing of SREBP, ATF6, CREB3 family members and other S1P substrates.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
POST1 modulates SREBP signaling by promoting Golgi localization of mature S1P.
“Further examination showed that POST1 modulated SREBP signaling by accelerating generation (Fig. 4) and Golgi localization (Fig. 5) of mature S1P.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationcitation
Defective lysosomal homeostasis in the absence of POST1 causes massive accumulation of cholesterol and LBPA in the cell.
“Defective lysosomal homeostasis in the absence of POST1 eventually caused massive accumulation of cholesterol and lyso-bis-phosphatidic acid (LBPA) in the cell (Fig. 6G and 6H), since lysosomal proteins such as NPC2 need M6P modification for lysosomal targeting (Wei et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wei et al., 2017 source
- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationreasoning
POST1 is required for S1P maturation.
“All their results can be explained by our finding that POST1 is required for S1P maturation.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Premisecitation
Lysosomal proteins such as NPC2 need M6P modification for lysosomal targeting.
“since lysosomal proteins such as NPC2 need M6P modification for lysosomal targeting (Wei et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wei et al., 2017 source
- Premisecitation
The prodomain of S1P is crucial for its folding, autoprocessing and proteolysis of substrates including SREBP2.
“Contrasting to those in other proprotein convertases that function as an inhibitor, the prodomain of S1P is crucial for its folding, autoprocessing and proteolysis of substrates including SREBP2 (da Palma et al., 2014; da Palma et al., 2016).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
POST1 is a cofactor of S1P.
“In summary, our study shows that POST1 is a cofactor of S1P.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
Survival of POST1-deficient cells in the AmB screen is attributable to defective lysosomal cholesterol transport resulting from impaired cleavage of the α/β-subunit precursor of GlcNAc-1-phosphotransferase.
“Based on these findings, we attribute the survival of POST1-deficient cells in the AmB screen to two reasons: 1) low LDLR expression as a result of impaired cleavage of SREBP2 (Figs. 2C and 3E); and 2) defective lysosomal cholesterol transport as a result of impaired cleavage of the α/β-subunit precursor of GlcNAc-1-phosphotransferase (Fig. 6C and 6G).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
Survival of POST1-deficient cells in the AmB screen is attributable to low LDLR expression resulting from impaired cleavage of SREBP2.
“Based on these findings, we attribute the survival of POST1-deficient cells in the AmB screen to two reasons: 1) low LDLR expression as a result of impaired cleavage of SREBP2 (Figs. 2C and 3E); and 2) defective lysosomal cholesterol transport as a result of impaired cleavage of the α/β-subunit precursor of GlcNAc-1-phosphotransferase (Fig. 6C and 6G).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
Less SCAP in POST1 KO cells is not the direct cause of impaired SREBP cleavage.
“So, less SCAP in POST1 KO cells is not the direct cause of impaired SREBP cleavage.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
Absence of POST1 impairs cleavage of ATF6 and CREB3L3.
“POST1 KO cells had less amounts of the cleaved nuclear form of ATF6 (n-ATF6) and CREB3L3 (n-CREB3L3) than WT cells, suggestive of impaired cleavage of ATF6 and CREB3L3 in the absence of POST1.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
POST1-mediated S1P maturation is critical for the cleavage of other S1P substrates including ATF6, CREB3L3 and the α/β-subunit precursor of GlcNAc-1-phosphotransferase.
“In addition to SREBP activation, POST1-mediated S1P maturation is also critical for the cleavage of other S1P substrates including ATF6, CREB3L3 and the α/β-subunit precursor of GlcNAc-1-phosphotransferase (Fig. 6).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationreasoning
POST1 promotes autocatalytic cleavage of S1P at the C'/C sites from immature S1P-A and S1P-B'/B.
“It promotes autocatalytic cleavage of S1P at the C’/C sites from immature S1P-A and S1P-B’/B.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
POST1 modulates SREBP signaling by accelerating generation of mature S1P.
“Further examination showed that POST1 modulated SREBP signaling by accelerating generation (Fig. 4) and Golgi localization (Fig. 5) of mature S1P.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- Interpretationown data
S1P-C'/C production absolutely depends on S1P enzymatic activity.
“However, this process is abolished by the D218A/H249A/S414A mutations (Fig. 4E), suggesting an absolute dependency on S1P enzymatic activity.”
Quote in the paperSubstantial claim- Rests on an assumption: The D218A/H249A/S414A mutations abolish S1P enzymatic activity.
- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
- It may state two separate claims as one. 20
- The quote only partly states this claim. 1
- Probably not a substantial claim. 7
It may state two separate claims as one.
Findingown dataPOST1 is predicted to contain a cytosolic segment (1-16 aa), a transmembrane segment (17-36 aa), and a 169-amino-acid lumenal stretch.
“It is predicted to contain a cytosolic segment (1–16 aa), a transmembrane segment (17–36 aa), and a stretch of 169 amino acids extending into the lumen (Fig. 1D).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataIn HA-1-transfected cells, S1P-A and a 14-kDa prodomain I band are detected; in HA-2-transfected cells, A and B'/B forms are detected.
“we detected S1P-A and a 14-kDa band corresponding in size to the prodomain I in the cells transfected with the HA-1 plasmid, but A and B’/B forms in the cells transfected with the HA-2 plasmid (lanes 3 and 5 of the 2nd and 3rd blots).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataThe C'/C mutant (CM, R163E/R164E/R183E/R184E) can generate S1P-B'/B but fails to yield S1P-C'/C.
“whereas the C’/C mutant (CM, R163E/R164E/R183E/R184E) could generate S1P-B’/B but failed to yield S1P-C’/C (lane 7).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataLoss of POST1 impairs the response of cholesterol biosynthetic genes (LSS, HMGCR, HMGCS1, SQLE, CYP51A1, FDFT1) and fatty acid biosynthetic genes (SCD1, FASN, ACC1), as well as INSIG1 and LDLR, to cholesterol depletion.
“loss of POST1 impaired the responses of cholesterol biosynthetic genes (lanosterol synthase [LSS], HMGCR, 3-hydroxy-3-methylglutaryl-CoA synthase 1 [HMGCS1], squalene epoxidase [SQLE], cytochrome P450 family 51 subfamily A member 1 [CYP51A1], farnesyl-diphosphate farnasyltransferase 1 [FDFT1]) and fatty acid biosynthetic genes (stearoyl-CoA desaturase 1 [SCD1], fatty acid synthase [FASN],”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn HeLa cells, POST1 staining colocalizes robustly with the Golgi marker GM130 and modestly with the ER marker DsRed-KDEL.
“We detected robust POST1 staining colocalized with GM130 and modest signal colocalized with DsRed-KDEL (Fig. 1E).”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingnone givenHuman POST1 is a small protein of 205 amino acids.
“Human POST1 is a small protein of 205 amino acids.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataTransfected POST1 protein is partially sensitive to Endo H and completely shifted to a lower position by PNGase F.
“The transfected POST1 protein was partially sensitive to endoglycosidase H (Endo H), but completely shifted to a lower position by peptide N-glycosidase F (PNGase F) (Fig. 1F).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataAt the protein level, LDLR and representative cholesterol biosynthetic enzymes are increased by cholesterol depletion and decreased by 25-HC, and to a lesser extent in POST1 knockout cells.
“At the protein level, the amounts of LDLR and representative cholesterol biosynthetic enzymes were similarly increased by cholesterol depletion and decreased by 25-HC, and in a lesser extent in POST1 KO cells (Fig. 2C).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSCAP and INSIG2 are not SREBP target genes and their expression remains unaltered regardless of treatment.
“SCAP and INSIG2 are not SREBP target genes and their expression remained unaltered regardless of treatments (Fig. 2B).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataCo-expression of POST1 increases S1P-C'/C production and eliminates S1P-B'/B.
“Co-expression of POST1 increased S1P-C’/C production and eliminated S1P-B’/B (Fig. 4D).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn the absence of POST1, the majority of S1P resides in the ER and only about 12% colocalizes with GM130.
“In the absence of POST1, the majority of S1P resided in the ER and only about 12% of S1P was found colocalized with GM130 (Fig. 5A and 5B).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataPOST1 facilitates the generation of S1P-C'/C that is subsequently transported to the Golgi.
“As these mutants (EM, BM and CM) produced little or no S1P-C’/C (Fig. 4E), it is concluded that POST1 facilitates the generation of S1P-C’/C that is subsequently transported to the Golgi.”
Quote in the paperSubstantial claimProbably not a substantial claim. It may state two separate claims as one.
PremisecitationAll S1P precursors reside in the ER and the mature S1P-C'/C resides in the Golgi.
“It is reported that all the S1P precursors reside in the ER and the mature S1P-C’/C resides in the Golgi (DeBose-Boyd et al., 1999).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites DeBose-Boyd et al., 1999 source
Probably not a substantial claim.
PremisecitationLysosome enlargement is a sign of dysfunction.
“Lysosome enlargement is a sign of dysfunction (te Vruchte et al., 2014; Xu et al., 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites te Vruchte et al., 2014 source
- cites Xu et al., 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim.
PremisecitationAutoprocessing at the C'/C sites occurs in trans involving another S1P protein.
“autoprocessing at the C’/C sites is reported to occur in trans involving another S1P protein (Espenshade et al., 1999; da Palma et al., 2014)”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationS1P-B'/B can already cleave the SREBP2 precursor and activate downstream signaling.
“Another unique aspect of S1P is that it needs not to be completely processed to become enzymatically active, as S1P-B’/B can already cleave the SREBP2 precursor and activate the downstream signaling (Espenshade et al., 1999; da Palma et al., 2014).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationATF6 and CREB3L3 are ER-resident proteins that respond to stimuli by trafficking to the Golgi where they are sequentially cleaved by S1P and S2P.
“Activating transcription factor 6 (ATF6) and cAMP response element–binding protein (CREB) 3 family members including CREB3L3 (also called CREBH) are ER-resident proteins that respond to stimuli by trafficking to the Golgi where they are sequentially cleaved by S1P and S2P (Ye et al., 2000; Zhang et al., 2006).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Ye et al., 2000
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Zhang et al., 2006 source
It may state two separate claims as one.
Interpretationown dataPOST1 is a key determinant for S1P maturation and lipid metabolism.
“These results set POST1 as a key determinant for S1P maturation and lipid metabolism.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
Probably not a substantial claim.
PremisecitationBFA disassembles and redistributes the Golgi complex into the ER.
“brefeldin A, an ER-Golgi protein trafficking inhibitor that disassembles and redistributes the Golgi complex into the ER (Sciaky et al., 1997).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sciaky et al., 1997 source
It may state two separate claims as one.
Interpretationown dataPOST1 is a S1P cofactor that promotes generation of S1P-C'/C, either from S1P-B'/B (canonical cleavage) or directly from S1P-A (non-canonical cleavage).
“Here, we demonstrate that POST1 is a S1P cofactor that promotes generation of S1P-C’/C, either from S1P-B’/B (canonical cleavage) or directly from S1P-A (non-canonical cleavage).”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
It may state two separate claims as one.
InterpretationcitationThe phenotypes of decreased SCAP protein level and SCAP relocation to the Golgi in C12ORF49 knockout are attributable to impairments in C12ORF49-mediated S1P maturation and defective SREBP cleavage.
“We believe that these phenotypes should be attributable to impairments in C12ORF49-mediated S1P maturation, and defective SREBP cleavage by S1P then prevents Golgi-to-ER transport of SCAP and causes SCAP degradation in lysosomes (Shao and Espenshade, 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Shao and Espenshade, 2014 source
- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
It may state two separate claims as one.
Interpretationown dataPOST1 accelerates generation of mature S1P-C'/C from S1P-B'/B via canonical cleavage and from S1P-A directly via non-canonical cleavage.
“Together, we propose that POST1 accelerates generation of mature S1P-C’/C from S1P-B’/B via a canonical cleavage as well as from S1P-A directly via a non-canonical cleavage (Fig. 6I).”
- Also stated in: § Abstract · plain
“POST1 promotes the generation of the functional S1P-C’/C from S1P-B’/B (canonical cleavage) and, notably, from S1P-A directly (non-canonical cleavage) as well.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
It may state two separate claims as one.
Interpretationown dataPOST1 facilitates S1P-C'/C production in the ER and then they are transported to Golgi together.
“These data suggest that POST1 facilitates S1P-C’/C production in the ER and then they are transported to Golgi together.”
Quote in the paperSubstantial claim- Rests on an assumption: The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
- Rests on an assumption: The antibodies used are specific for their targets.
- Rests on an assumption: The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
It may state two separate claims as one.
Interpretationown dataPOST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism, and lysosome biogenesis.
“Together, we demonstrate that POST1 is a cofactor controlling S1P maturation and plays important roles in lipid homeostasis, unfolded protein response, lipoprotein metabolism and lysosome biogenesis.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataPOST1 promotes self-cleavage of S1P in the ER and the generated S1P-C'/C still binds to POST1.
“These results indicate that POST1 promotes self-cleavage of S1P in the ER and that the generated S1P-C’/C still binds to POST1.”
Quote in the paperSubstantial claim
The paper relies on this without support.
How S1P cleavage at the Golgi is regulated is less clear than how SREBP precursor localization is regulated.
“Compared with the above mechanisms controlling localization of the SREBP precursor, how its cleavage at the Golgi is regulated is less clear.”
The paper relies on this without support.
Whether and how S1P autoprocessing is regulated is largely unknown.
“Despite the understanding of S1P autoprocessing, little is known whether and how, if any, this process is regulated.”
The paper relies on this without support.
The D218A/H249A/S414A mutations abolish S1P enzymatic activity.
“this process is abolished by the D218A/H249A/S414A mutations (Fig. 4E), suggesting an absolute dependency on S1P enzymatic activity.”
The paper relies on this without support.
The AmB selection challenge enriches for genes involved in LDL uptake and cholesterol trafficking to the PM.
“we performed a genome-scale, unbiased CRISPR/Cas9 KO screen coupled to the “cholesterol depletion-repletion-AmB selection” challenge (Fig. 1A), so that genes involved in LDL uptake and cholesterol trafficking to the PM were highly enriched.”
The paper relies on this without support.
The sgRNAs used to generate POST1 KO and S1P KO cells specifically and effectively knock out their targets.
“HeLa/POST1 KO cells and HeLa/S1P KO cells were generated using the CRISPR-Cas9 technology (sgRNAs listed in Supplementary Material, Table S4) and isolated by limiting dilution analysis.”
The paper relies on this without support.
The antibodies used are specific for their targets.
“Primary antibodies were used at the dilution of 1:500 for immunofluorescent staining and 1:1,000 for immunoblotting.”
The paper relies on this without support.
The observed phenotypes in POST1 KO cells are due to loss of POST1 and not off-target effects.
“HeLa/POST1 KO cells and HeLa/S1P KO cells were generated using the CRISPR-Cas9 technology (sgRNAs listed in Supplementary Material, Table S4) and isolated by limiting dilution analysis.”
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?
The proteolytic activation of S1P into its mature Golgi-associated form is attenuated in SPRING-deficient cells.
“Additionally, the proteolytic activation of S1P into its mature Golgi-associated form is attenuated13,14.”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [13]
Spring enhances the proteolytic maturation of S1P.
“our study and that by Xiao et al. recently demonstrated that Spring enhances the proteolytic maturation of S1P (encoded by Mbtps1)13,14”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [13]
In cultured cells, SPRING is implicated in the retrograde transport of SCAP.
“We and others have proposed that, in cultured cells, SPRING is implicated in two important regulatory steps in the SREBP pathway, i.e. the retrograde transport of SCAP and in regulating the activity of S1P10–13.”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [13]
In cultured cells, SPRING is implicated in regulating the activity of S1P.
“We and others have proposed that, in cultured cells, SPRING is implicated in two important regulatory steps in the SREBP pathway, i.e. the retrograde transport of SCAP and in regulating the activity of S1P10–13.”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [13]
The SPRING cysteine-rich domain is necessary and sufficient for interacting with S1P and SCAP, and for promoting S1P proteolytic maturation and restoration of SREBP signaling in SPRINGKO cells.
“which is both necessary and sufficient for interacting with S1P12–14 and SCAP10, and for promoting S1P proteolytic maturation and restoration of SREBP signaling in SPRINGKO cells14”
From Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans (2023) · cites this paper as [13]
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.
Figure 6 quantification identifies different cells from its source panels
MinorThe caption says panel H quantifies HeLa and POST1-knockout cells shown in panels F and G, but both source panels are described as HeLa cells transfected with siRNAs, not knockout cells.
“(H) Quantification of filipin, Lysotracker and LBPA intensity in HeLa and HeLa/POST1 KO cells shown in (F) and (G).”
“(F) HeLa cells were transfected with the indicated siRNAs for 48 h, and stained with Lysotracker (red) for 30 min. Cells were then fixed and immunostained with the antibodies against LAMP1 (green). Scale bar, 10 μm. (G) HeLa cells were transfected with the indicated siRNAs for 48 h”
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Metadata
- Authors
- Xiao, J., Xiong, Y., Yang, L.-T., Wang, J.-Q., Zhou, Z.-M., Dong, L.-W., Shi, X.-J., Zhao, X., Luo, J., & Song, B.-L.
- Affiliations
- Wuhan University (CN)
- Corresponding author
- Luo, Jie
- Song, Bao-Liang
- Venue
- Protein & Cell
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-07-14
- Volume
- 12
- Issue
- 4
- Pages
- 279-296
- ISSN
- 1674-800X (ISSN-L)
- 1674-8018
- PMC
- PMC8019017
- OpenAlex
- W3043522585
- Semantic Scholar
- 069536c736bdc9134005c053004f6f98ea866741
- Cited by
- 49
- References
- 45
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 5 · 2023: 18 · 2022: 7 · 2021: 4 · 2020: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Protein & Cell (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Tencent
- National Natural Science Foundation of China (111 Project, 91954203, 31690102, 31771568, 91754102, 2016YFA0500100)
- Ministry of Education of the People's Republic of China (B16036, ‘111’ Project)
- Higher Education Discipline Innovation Project
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- site-1 protease, SREBP signaling, cholesterol metabolism, lipid homeostasis, unfolded protein response, lipoprotein metabolism, lysosomal biogenesis, ATF6, CREB3, N-acetylglucosamine-1-phosphotransferase, protease maturation, Golgi apparatus
- MeSH terms
- HeLa Cells, Humans, Lipoproteins, Lysosomes, Membrane Proteins, Signal Transduction, Sterol Regulatory Element Binding Proteins, CRISPR-Cas Systems
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