The 26S proteasome is responsible for most regulated protein turnover and for the degradation of aberrant proteins in eukaryotes. The assembly of this ~2.5 MDa multicatalytic protease requires several dedicated chaperones and, once assembled, substrate selectivity is mediated by ubiquitin conjugation. After modification with ubiquitin, substrates are escorted to the proteasome by myriad factors, including Cdc48 (cell-division cycle 48). Cdc48 also associates with numerous cofactors, but, to date, it is unclear whether each cofactor facilitates proteasome delivery. We discovered that yeast lacking a conserved Cdc48 cofactor, Vms1 [VCP (valosin-containing protein)/Cdc48-associated mitochondrial stress-responsive], accumulate proteasome-targeted ubiquitinated proteins. Vms1 mutant cells also contain elevated levels of unassembled 20S proteasome core particles and select 19S cap subunits. In addition, we found that the ability of Vms1 to support 26S proteasome assembly requires Cdc48 interaction, and that the loss of Vms1 reduced 26S proteasome levels and cell viability after prolonged culture in the stationary phase. The results of the present study highlight an unexpected link between the Cdc48–Vms1 complex and the preservation of proteasome architecture, and indicate how perturbed proteasome assembly affects the turnover of ubiquitinated proteins and maintains viability in aging cells.
Skip Nav Destination
Article navigation
March 2014
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 28 2014
The Cdc48–Vms1 complex maintains 26S proteasome architecture
Joseph R. Tran;
Joseph R. Tran
1
*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
†Graduate Program in Biochemistry and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, U.S.A.
Search for other works by this author on:
Jeffrey L. Brodsky
Jeffrey L. Brodsky
2
*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
2To whom correspondence should be addressed (email jbrodsky@pitt.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 27 2013
Revision Received:
December 12 2013
Accepted:
December 19 2013
Accepted Manuscript online:
December 19 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 458 (3): 459–467.
Article history
Received:
August 27 2013
Revision Received:
December 12 2013
Accepted:
December 19 2013
Accepted Manuscript online:
December 19 2013
Citation
Joseph R. Tran, Jeffrey L. Brodsky; The Cdc48–Vms1 complex maintains 26S proteasome architecture. Biochem J 15 March 2014; 458 (3): 459–467. doi: https://doi.org/10.1042/BJ20131161
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.