Regulation of cellular functions by chaperone-like AAA-ATPases, VCP and NVL
| Project/Area Number |
15570166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
NAGAHAMA Masami Tokyo University of Pharmacy and Life Science, School of Life Science, Research Associate, 生命科学部, 助手 (60281169)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | chaperone / ERAD / ribosome / nucleolus / 分子シャペロン / アダプター |
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| Research Abstract |
VCP is an AAA-ATPase, which plays critical roles for cellular functions such as endoplasmic reticulum associated degradation(ERAD) and organella biogenesis. SVIP has been identified as a VCP-interacting protein, whose expression causes cell vacuolation by expansion of ER. To clarify a cellular function of SVIP, we first investigated a role of SVIP for ERAD by employing assays in virto and in vivo. The results from both the assays showed that extra amount of SVIP inhibits ERAD and this may be a cause of the ER vacuolation. Next, to identify other protein components involved in the VCP-SVIP complex, yeast two-hybrid screening was performed using entire SVIP as a bait As a result, several cDNAs encoding putative SVIP-associated proteins were obtained.
NVL2 is a protein that shows high amino acid similarity with VCP. In contrast to mainly cytosolic distribution of VCP, localization of NVL2 is restricted to the nucleolus, suggesting a specialized role of NVL2 in this nuclear subcompartment. In this research, we showed that NVL2 interacts with a RNA helicase and is involved in biogenesis of 60S ribosomes. Although expression of a dominant-negative mutant of NVL2 did not affect rRNA processing, it caused accumulation of the helicase in a large complex, probably a pre-ribosomal particle. Additionally, mutagenesis studies identified a nucleolar localization signal in NVL2. This signal is required for the binding of NVL2 with ribosomal protein L5,suggesting that NVL2 is recruited to the nucleolus by associating with L5.
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Report
(3 results)
Research Products
(2 results)
