Ee. Patton et al., CDC53 IS A SCAFFOLD PROTEIN FOR MULTIPLE CDC34 SKP1/F-BOX PROTEIN COMPLEXES THAT REGULATE CELL-DIVISION AND METHIONINE BIOSYNTHESIS IN YEAST/, Genes & development, 12(5), 1998, pp. 692-705
In budding yeast, ubiquitination of the cyclin-dependent kinase (Cdk)
inhibitor Sic1 is catalyzed by the E2 ubiquitin conjugating enzyme Cdc
34 in conjunction with an E3 ubiquitin ligase complex composed of Skp1
, Cdc53 and the F-box protein, Cdc4 (the SCECdc4 complex). Skp1 binds
a motif called the F-box and in turn E-box proteins appear to recruit
specific substrates for ubiquitination. We find that Skp1 interacts wi
th Cdc53 in vivo, and that Skp1 bridges Cdc53 to three different F-box
proteins, Cdc4, Met30, and Grr1. Cdc53 contains independent binding s
ites for Cdc34 and Skp1 suggesting it functions as a scaffold protein
within an E2/E3 core complex. E-box proteins show remarkable functiona
l specificity in vivo: Cdc4 is specific for degradation of Sic1, Grr1
is specific for degradation of the G(1) cyclin Cln2, and Met30 is spec
ific for repression of methionine biosynthesis genes. In contrast, the
Cdc34-Cdc53-Skp1 E2/E3 core complex is required for all three functio
ns. Combinatorial control of SCE complexes may provide a basis for the
regulation of diverse cellular processes.