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Genes Dev

Title:		Phosphorylation- and ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor Far1p in budding yeast
Author(s):		Henchoz S; Chi Y; Catarin B; Herskowitz I; Deshaies RJ; Peter M;
Address:		"Institut Suisse de Rechereches Experimentales sur le Cancer (ISREC), 1066 Epalinges/VD Switzerland"
Journal Title:		Genes Dev
Year:		1997
Volume:		11
Issue:		22
Page Number:		3046 - 3060
DOI:		10.1101/gad.11.22.3046
ISSN/ISBN:		0890-9369 (Print) 0890-9369 (Linking)
Abstract:		"Cyclin-dependent kinase inhibitors (CKIs) play key roles in controlling the eukaryotic cell cycle by coordinating cell proliferation and differentiation. Understanding the roles of CKIs requires knowledge of how they are regulated both through the cell cycle and in response to extracellular signals. Here we show that the yeast CKI, Far1p, is controlled by ubiquitin-dependent proteolysis. Wild-type Far1p was stable only in the G1 phase of the cell cycle. Biochemical and genetic evidence indicate that its degradation required the components of the G1-S ubiquitination system, Cdc34p, Cdc4p, Cdc53p, and Skp1p. We isolated a mutant form of Far1p (Far1p-22) that was able to induce cell cycle arrest in the absence of alpha-factor. Cells that overexpress Far1-22p arrested in G1 as large unbudded cells with low Cdc28p-Clnp kinase activity. Wild-type Far1p, but not Far1-22p, was readily ubiquitinated in vitro in a CDC34- and CDC4-dependent manner. Far1-22p harbors a single amino acid change, from serine to proline at residue 87, which alters phosphorylation by Cdc28p-Cln2p in vitro. Our results show that Far1p is regulated by ubiquitin-mediated proteolysis and suggest that phosphorylation of Far1p by the Cdc28p-Clnp kinase is part of the recognition signal for ubiquitination"
Keywords:		"Anaphase-Promoting Complex-Cyclosome CDC28 Protein Kinase, S cerevisiae/metabolism *Cell Cycle Cell Cycle Proteins/*metabolism Cyclin-Dependent Kinase Inhibitor Proteins Cyclins/metabolism Cysteine Endopeptidases/metabolism *F-Box Proteins Fungal Proteins;"
Notes:		"MedlineHenchoz, S Chi, Y Catarin, B Herskowitz, I Deshaies, R J Peter, M eng GM 52466-01/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. 1997/12/31 Genes Dev. 1997 Nov 15; 11(22):3046-60. doi: 10.1101/gad.11.22.3046"