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Vol. 11, Issue 3, 915-927, March 2000
*Department of Microbiology, Technion-B. Rappaport
Faculty of Medicine, Haifa 31096, Israel; 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.
Department of
Oncological Sciences, University of Utah, Salt Lake City, Utah 84132;
and §Whitehead Institute, Cambridge, Massachusetts 02142
Present address: Beckman Institute,
California Institute of Technology, Pasadena, CA 91125.
Corresponding author. E-mail address:
danielk{at}tx.technion.ac.il.
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