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 ns 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, aad the early returns from genetic analysis in several organisms promise that F-box proteins will participate ill the regulation of many processes, including cell division transcription, signal transduction and development.