Article: article from journal or magazin.
Ubiquitin-dependent degradation of multiple F-box proteins by an autocatalytic mechanism.
Proceedings of the National Academy of Sciences of the United States of America
Ubiquitin-dependent degradation of regulatory proteins controls many cellular processes, including cell cycle progression, morphogenesis, and signal transduction. Skp1p-cullin-F-box protein (SCF) complexes are ubiquitin ligases composed of a core complex including Skp1p, Cdc53p, one of multiple F-box proteins that are thought to provide substrate specificity to the complex, and the ubiquitin-conjugating enzyme, Cdc34p. It is not understood how SCF complexes are regulated and how physiological conditions alter their levels. Here we show that three F-box proteins, Grr1p, Cdc4p, and Met30p, are unstable components of the SCF, and are themselves degraded in a ubiquitin- and proteasome-dependent manner in vivo. Ubiquitination requires all the core components of the SCF and an intact F-box, suggesting that ubiquitination occurs within the SCF complex by an autocatalytic mechanism. Cdc4p and Grr1p are intrinsically unstable, and their steady-state levels did not fluctuate through the cell cycle. Taken together, our results suggest that ubiquitin-dependent degradation of F-box proteins allows rapid switching among multiple SCF complexes, thereby enabling cells to adapt quickly to changing physiological conditions and progression through different phases of the cell cycle.
Catalysis, Cell Cycle/physiology, Cell Cycle Proteins/metabolism, F-Box Proteins, Fungal Proteins/metabolism, Genotype, Peptide Synthases/metabolism, Repressor Proteins/metabolism, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae/cytology, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae Proteins, Substrate Specificity, Trans-Activators/metabolism, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Ubiquitins/metabolism
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