ArticleMolecular & cellular proteomics : MCP2018
AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Induced degradation of Ufd1 reveals regulation of cohesin by the VCP/p97Life science alliance · 2026Article
- The accessory adapters FAF1, FAF2, and UBXN7 accelerate proteasomal degradation by increasing prior p97-mediated substrate unfolding.Science advances · 2026Article
- Raphin-1 mediates the survival and sensitivity to radiation of pediatric-type diffuse high-grade glioma via phosphorylated eukaryotic initiation factor 2α-dependent and -independent processes.Molecular oncology · 2025Article
- ATXN3 regulates lysosome regeneration after damage by targeting K48-K63-branched ubiquitin chains.The EMBO journal · 2025Article
- Selenoprotein K Is a Peripheral ER Membrane Protein.Biochemistry · 2025Article
- Based exploration of the diagnostic value of oxidative stress-related key genes in chronic obstructive pulmonary disease.Cell biology and toxicology · 2025Article
- Selenoprotein K at the intersection of cellular pathways.Archives of biochemistry and biophysics · 2025Review
- A guide to selecting high-performing antibodies for VCP (UniProt ID: P55072) for use in western blot, immunoprecipitation, and immunofluorescence.F1000Research · 2025Article
- Human VCP mutant ALS/FTD microglia display immune and lysosomal phenotypes independently of GPNMB.Molecular neurodegeneration · 2024Article
- VCP/p97 mediates nuclear targeting of non-ER-imported prion protein to maintain proteostasis.Life science alliance · 2024Article
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA.The Journal of cell biology · 2023Article
- Article
- Order through destruction: how ER-associated protein degradation contributes to organelle homeostasis.The EMBO journal · 2022Review
- Quality Control of ER Membrane Proteins by the RNF185/Membralin Ubiquitin Ligase Complex.Molecular cell · 2020Article
- Article
- CReP mediates selective translation initiation at the endoplasmic reticulum.Science advances · 2020Article
- Mitochondrial MUL1 E3 ubiquitin ligase regulates Hypoxia Inducible Factor (HIF-1α) and metabolic reprogramming by modulating the UBXN7 cofactor protein.Scientific reports · 2020Article
- The ubiquitin-conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage.EMBO reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of its interactions with partner and substrate proteins and understanding its links to stress signaling is therefore a major challenge. Here, we used affinity-purification SWATH mass spectrometry (AP-SWATH) to identify proteins that specifically interact with the substrate-trapping mutant, p97-E578Q. AP-SWATH identified differential interactions over a large detection range from abundant p97 cofactors to pathway-specific partners and individual ligases such as RNF185 and MUL1 that were trapped in p97-E578Q complexes. In addition, we identified various substrate proteins and candidates including the PP1 regulator CReP/PPP1R15B that dephosphorylates eIF2α and thus counteracts attenuation of translation by stress-kinases. We provide evidence that p97 with its Ufd1-Npl4 adapter ensures rapid constitutive turnover and balanced levels of CReP in unperturbed cells. Moreover, we show that p97-mediated degradation, together with a reduction in CReP synthesis, is essential for timely stress-induced reduction of CReP levels and, consequently, for robust eIF2α phosphorylation to enforce the stress response. Thus, our results demonstrate that p97 not only facilitates bulk degradation of misfolded proteins upon stress, but also directly modulates the integrated stress response at the level of signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.