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Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae

Ghislain, Michel and Dohmen, R. Jürgen and Lévy, Frédéric and Varshavsky, Alexander (1996) Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin-mediated proteolysis in Saccharomyces cerevisiae. EMBO Journal, 15 (18). pp. 4884-4899. ISSN 0261-4189. PMCID PMC452226. doi:10.1002/j.1460-2075.1996.tb00869.x.

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A library of random 10 residue peptides fused to the N‐terminus of a reporter protein was screened in the yeast Saccharomyces cerevisiae for sequences that can target the reporter for degradation by the N‐end rule pathway, a ubiquitin (Ub)‐dependent proteolytic system that recognizes potential substrates through binding to their destabilizing N‐terminal residues. One of the N‐terminal sequences identified by this screen was used in a second screen for mutants incapable of degrading the corresponding reporter fusion. A mutant thus identified had an abnormally low content of free Ub. This mutant was found to be allelic to a previously isolated mutant in a Ub‐dependent proteolytic system distinct from the N‐end rule pathway. We isolated the gene involved, termed UFD3, which encodes an 80 kDa protein containing tandem repeats of a motif that is present in many eukaryotic proteins and called the WD repeat. Both co‐immunoprecipitation and two‐hybrid assays demonstrated that Ufd3p is an in vivo ligand of Cdc48p, an essential ATPase required for the cell cycle progression and the fusion of endoplasmic reticulum membranes. Further, we showed that, similarly to Ufd3p, Cdc48p is also required for the Ub‐dependent proteolysis of test substrates. The discovery of the Ufd3p–Cdc48p complex and the finding that this complex is a part of the Ub system open up a new direction for studies of the function of Ub in the cell cycle and membrane dynamics.

Item Type:Article
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URLURL TypeDescription CentralArticle
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 1996 European Molecular Biology Organization. Received on April 3, 1996; revised on June 11, 1996. We thank A.Webster for comparing the sequences of N-terminal extensions: colleagues cited in the paper, especially K.Madura, E.Andrews, E.S.Johnson, T.W.Chritianson and J.Mulhollaw for strains and/or plasmids: and W.Lane (Harvard Microchemistry Facility) for protein sequencing. This work was supported by grants to A.V. from the National Institutes of Health (GM31530 and DK39520). M.G. and F.L. were supported by postdoctoral fellowships from, respectively, the Human Frontier Science Program and the Swiss National Fund for Research.
Funding AgencyGrant Number
Human Frontier Science ProgramUNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
Subject Keywords:cell cycle/N-end rule/proteolysis/ubiquitin/WD repeat
Issue or Number:18
PubMed Central ID:PMC452226
Record Number:CaltechAUTHORS:20210211-162600585
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Official Citation:Ghislain, M., Dohmen, R.J., Levy, F. and Varshavsky, A. (1996), Cdc48p interacts with Ufd3p, a WD repeat protein required for ubiquitin‐mediated proteolysis in Saccharomyces cerevisiae. The EMBO Journal, 15: 4884-4899.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108026
Deposited By: George Porter
Deposited On:12 Feb 2021 16:33
Last Modified:16 Nov 2021 19:08

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