ArticleThe Journal of biological chemistry2013
Interaction between salt-inducible kinase 2 (SIK2) and p97/valosin-containing protein (VCP) regulates endoplasmic reticulum (ER)-associated protein degradation in mammalian cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Salt-inducible kinase 2 confers radioresistance in colorectal cancer by facilitating homologous recombination repair.MedComm · 2025Article
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- Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency.Cell death discovery · 2022Article
- Genome-Wide Profiling of Acquired Uniparental Disomy Reveals Prognostic Factors in Head and Neck Squamous Cell Carcinoma.Neoplasia (New York, N.Y.) · 2019Article
- The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97.Frontiers in molecular biosciences · 2017Review
- The fine-tuning of proteolytic pathways in Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2016Review
- Activation of salt-inducible kinase 2 promotes the viability of peritoneal mesothelial cells exposed to stress of peritoneal dialysis.Cell death & disease · 2016Article
- IBMPFD Disease-Causing Mutant VCP/p97 Proteins Are Targets of Autophagic-Lysosomal Degradation.PloS one · 2016Article
- Structural insight into the mechanism of synergistic autoinhibition of SAD kinases.Nature communications · 2015Article
- Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element-binding protein-mediated gene expression in various cell types and is the only AMP-activated protein kinase family member known to interact with the p97/valosin-containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can regulate autophagy when proteasomal function is compromised. Here we report that physical and functional interactions between SIK2 and p97/VCP underlie the regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD). SIK2 co-localizes with p97/VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation. Although the expression of wild-type recombinant SIK2 accelerated the degradation and removal of ERAD substrates, the kinase-deficient variant conversely had no effect. Furthermore, down-regulation of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired degradation of ERAD substrates and disruption of ER homeostasis. Collectively, these findings highlight a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells.
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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.