SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation
Open accessAbstract
VCP/p97 is involved in a variety of cellular processes, including membrane fusion and ubiquitin-dependent protein degradation. It has been suggested that adaptor proteins such as p47 and Ufd1p confer functional versatility to VCP/p97. To identify novel adaptors, we searched for proteins that interact specifically with VCP/p97 by using the yeast two-hybrid system, and discovered a novel VCP/p97-interacting protein named smallVCP/p97-interactingprotein (SVIP). Rat SVIP is a 76-amino acid protein that contains two putative coiled-coil regions, and potential myristoylation and palmitoylation sites at the N terminus. Binding experiments revealed that the N-terminal coiled-coil region of SVIP, and the N-terminal and subsequent ATP-binding regions (ND1 domain) of VCP/p97, interact with each other. SVIP and previously identified adaptors p47 and ufd1p interact with VCP/p97 in a mutually exclusive manner. Overexpression of full-length SVIP or a truncated mutant did not markedly affect the structure of the Golgi apparatus, but caused extensive cell vacuolation reminiscent of that seen upon the expression of VCP/p97 mutants or polyglutamine proteins in neuronal cells. The vacuoles seemed to be derived from endoplasmic reticulum membranes. These results together suggest that SVIP is a novelVCP/p97 adaptor whose function is related to the integrity of the endoplasmic reticulum.
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Disturbance of ER homeostasis in cEDS is suggested by the decreased transcription of SVIP.
“The disturbance of ER homeostasis in cEDS is also suggested by the decreased transcription of the small VCP/p97-interacting protein (SVIP), which is a modulator of the ER-associated degradation pathway [86,87].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [86]
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SVIP Induces Localization of p97/VCP to the Plasma and Lysosomal Membranes and Regulates Autophagy
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- Authors
- Nagahama, M., Suzuki, M., Hamada, Y., Hatsuzawa, K., Tani, K., Yamamoto, A., & Tagaya, M.
- Affiliations
- Tokyo University of Pharmacy and Life Sciences (JP)
- Kansai Medical University (JP)
- Venue
- Molecular Biology of the Cell
- Published
- 2003-01
- Volume
- 14
- Issue
- 1
- Pages
- 262-273
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC140243
- OpenAlex
- W2160545452
- Cited by
- 95
- References
- 62
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 2 · 2021: 1 · 2019: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2013: 5 · 2012: 2
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (11480183, 10215205)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- VCP/p97, protein-protein interaction, coiled-coil domain, vacuolization, Golgi apparatus, p47phox, polyglutamine proteins, myristoylation, palmitoylation, ATP-binding domain
- MeSH terms
- Animals, Endoplasmic Reticulum, Nuclear Proteins, Protein Binding, Vacuoles, Protozoan Proteins, Two-Hybrid System Techniques, Rats
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