SCF ubiquitin protein ligases and phosphorylation-dependent proteolysis

Many key activators and inhibitors of cell division are targeted for degrad ation by a recently described family of E3 ubiquitin protein ligases termed Skpl-Cdc53-F-box protein (SCF) complexes. SCF complexes physically link su bstrate proteins to the E2 ubiquitin-conjugating enzyme Cdc34, which cataly ses substrate ubiquitination, leading to subsequent degradation by the 26S proteasome. SCF complexes contain a variable subunit called an F-box protei n that confers substrate specificity on an invariant core complex composed of the subunits Cdc34, Skpl and Cdc53. Here, we review the substrates and p athways regulated by the yeast F-box proteins Cdc4, Grrl and Met30. The con cepts of SCF ubiquitin ligase function are illustrated by analysis of the d egradation pathway for the G1 cyclin Cln2. Through mass spectrometric analy sis of Cdc53 associated proteins, we have identified three novel F-box prot eins that appear to participate in SCF-like complexes. As many F-box protei ns can be found in sequence databases, it appears that a host of cellular p athways will be regulated by SCF-dependent proteolysis.