Targeted Proteolysis at GlS

The hgases involved in this type of ubiquitin ligation are organized in multiprotein complexes caUed SCF complexes (Skpl, cuUin, F box protein). In S. cerevisiae, the complex is composed of the proteins Cdc24 (an E2 enzyme), Cdc53 and Skpl, which form the core of the SCF. This core associates in a variable maimer with a further type of protein, which function as specific substrate recognition factors. A common feature of these proteins is a sequence element known as the F box (review Peters, 1998). Consequently, multiple forms of SCF complexes exist, due to this variable association. 

Substrate proteins are selected for Ub hgation based on a C-terminal target sequence. These sequences which, due to the occurrence of common amino acids, are known as PEST sequences, are targets for phosphorylation. In the phosphorylated form, they are recognized by the ubiquitin hgase complex and marked for degradation. 

Examples of Ub-mediated degradation of ceU cycle contiol proteins are  

an inhibitor of B type cychn/CDKl complexes the inhibitor p27  

For the G1 cyclins in yeast, it is assumed that they are phosphorylated in an autocataly-tic process by the activated Gl-cyclin-CDK complex and are thus marked for degradation. According to this mechanism, the G1 cyclins are subject to continual degradation, which would explain their short half-hfe. 

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