Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis.
The ubiquitin-dependent proteolytic pathway targets many key regulatory proteins for rapid intracellular degradation. Specificity in protein ubiquitination derives from E3 ubiquitin protein ligases, which recognize substrate proteins. Recently, analysis of the E3s that regulate cell division has revealed common themes in structure and function. One particularly versatile class of E3s, referred to as Skp1p-Cdc53p-F-box protein (SCF) complexes, utilizes substrate-specific adaptor subunits called F-box proteins to recruit various substrates to a core ubiquitination complex. A vast array of F-box proteins have been revealed by genome sequencing projects, and the early returns from genetic analysis in several organisms promise that F-box proteins will participate in the regulation of many processes, including cell division, transcription, signal transduction and development.
Patton
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Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Willems
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Tyers
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D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000502:physiology*; D029968:Escherichia coli Proteins; D006801:Humans; D008025:Ligases / Q000502:physiology*; D018832:Molecular Chaperones; D015398:Signal Transduction; D013379:Substrate Specificity; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000502:physiology*; D015003:Yeasts
D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D014452:Ubiquitins; C072721:Skp protein, E coli; D044767:Ubiquitin-Protein Ligases; D008025:Ligases