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Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCFCDC4 ubiquitin-ligase complex

Meimoun, Ariella and Holtzman, Tsvi and Weissman, Ziva and McBride, Helen J. and Stillman, David J. and Fink, Gerald R. and Kornitzer, Daniel (2000) Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCFCDC4 ubiquitin-ligase complex. Molecular Biology of the Cell, 11 (3). pp. 915-927. ISSN 1059-1524. PMCID PMC14820.

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Gcn4, a yeast transcriptional activator that promotes the expression of amino acid and purine biosynthesis genes, is rapidly degraded in rich medium. Here we report that SCFCDC4, a recently characterized protein complex that acts in conjunction with the ubiquitin-conjugating enzyme Cdc34 to degrade cell cycle regulators, is also necessary for the degradation of the transcription factor Gcn4. Degradation of Gcn4 occurs throughout the cell cycle, whereas degradation of the known cell cycle substrates of Cdc34/SCFCDC4 is cell cycle regulated. Gcn4 ubiquitination and degradation are regulated by starvation for amino acids, whereas the degradation of the cell cycle substrates of Cdc34/SCFCDC4 is unaffected by starvation. We further show that unlike the cell cycle substrates of Cdc34/SCFCDC4, which require phosphorylation by the kinase Cdc28, Gcn4 degradation requires the kinase Pho85. We identify the critical target site of Pho85 on Gcn4; a mutation of this site stabilizes the protein. A specific Pho85-Pcl complex that is able to phosphorylate Gcn4 on that site is inactive under conditions under which Gcn4 is stable. Thus, Cdc34/SCFCDC4 activity is constitutive, and regulation of the stability of its various substrates occurs at the level of their phosphorylation.

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Additional Information:Copyright © 2000 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license ( Submitted June 21, 1999; revised November 4, 1999; accepted January 4, 2000. We thank Masafumi Nishizawa, Mike Tyers, Steve Elledge, Wade Harper, Steve Buratowski, Angelika Amon, Phil Hieter, Brenda Andrews, Helen Causton, Gerard Faye, and Curt Wittenberg for strains and plasmids; Mike Tyers for the Sic1 antibody; and Aaron Ciechanover and Sara Selig for critical reading of the manuscript. This work was supported by grants from the Israel Science Foundation and the Israel Cancer Research Fund to D.K., National Institutes of Health (NIH) grants GM35010 to G.R.F. and GM48624 and GM39067 to D.J.S., and NIH training grant GM07464 to H.J.M.
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Israeli Science FoundationUNSPECIFIED
Israel Cancer Research FundUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC14820
Record Number:CaltechAUTHORS:MEImbc00
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5670
Deposited By: Lindsay Cleary
Deposited On:27 Oct 2006
Last Modified:02 Oct 2019 23:25

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