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J Biol Chem

Title:		Regulation of Ste7 ubiquitination by Ste11 phosphorylation and the Skp1-Cullin-F-box complex
Author(s):		Wang Y; Ge Q; Houston D; Thorner J; Errede B; Dohlman HG;
Address:		"Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-2852, USA"
Journal Title:		J Biol Chem
Year:		2003
Volume:		20030331
Issue:		25
Page Number:		22284 - 22289
DOI:		10.1074/jbc.M301272200
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"Ste7 is a mitogen-activated protein kinase kinase that mediates pheromone signaling in Saccharomyces cerevisiae. We showed previously that Ste7 is ubiquitinated upon prolonged stimulation by pheromone and that accumulation of ubiquitinated Ste7 results in enhanced transcription and cell division arrest responses (Wang, Y., and Dohlman, H. G. (2002) J. Biol. Chem. 277, 15766-15772). We now report that ubiquitination of Ste7 requires Ste11 kinase and Skp1/Cullin/F-box (SCF) ubiquitin-conjugating activities. Ste7 is not ubiquitinated in Ste11-deficient cells or when the Ste11 phosphorylation sites have been mutated. Ste7 ubiquitination and degradation (but not phosphorylation) is specifically blocked in mutants defective for the E2 ubiquitin-conjugating enzyme Cdc34 or the cullin homologue Cdc53. Both are components of the SCF complex that ubiquitinates proteins during the G1-S transition of the cell cycle. Our findings suggest that SCF promotes the ubiquitination and degradation of Ste7, thereby favoring the resumption of cell division cycling after pheromone-induced growth arrest"
Keywords:		Cell Cycle Proteins/genetics/*metabolism Genotype Ligases/metabolism Mitogen-Activated Protein Kinase Kinases Pheromones/pharmacology/physiology Plasmids Protein Kinases/genetics/*metabolism S-Phase Kinase-Associated Proteins Saccharomyces cerevisiae/drug;
Notes:		"MedlineWang, Yuqi Ge, Qing Houston, Dayle Thorner, Jeremy Errede, Beverly Dohlman, Henrik G eng R01 GM055316/GM/NIGMS NIH HHS/ GM021841/GM/NIGMS NIH HHS/ R01 GM059167/GM/NIGMS NIH HHS/ GM59167/GM/NIGMS NIH HHS/ GM55316/GM/NIGMS NIH HHS/ GM39582/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2003/04/02 J Biol Chem. 2003 Jun 20; 278(25):22284-9. doi: 10.1074/jbc.M301272200. Epub 2003 Mar 31"