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Association of human CUL‐1 and ubiquitin‐conjugating enzyme CDC34 with the F‐box protein p45 SKP2 : evidence for evolutionary conservation in the subunit composition of the CDC34–SCF pathway
Author(s) -
Lisztwan Joanna,
Marti Alain,
Sutterlüty Hedwig,
Gstaiger Matthias,
Wirbelauer Christiane,
Krek Wilhelm
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.2.368
Subject(s) - skp1 , ubiquitin ligase , biology , cell division control protein 4 , skp2 , cullin , ubiquitin , ubiquitin conjugating enzyme , cyclin dependent kinase , microbiology and biotechnology , cyclin dependent kinase complex , cyclin a , protein subunit , biochemistry , cell cycle , cell , gene
In normal and transformed cells, the F‐box protein p45 SKP2 is required for S phase and forms stable complexes with p19 SKP1 and cyclin A–cyclin‐dependent kinase (CDK)2. Here we identify human CUL‐1, a member of the cullin family, and the ubiquitin‐conjugating enzyme CDC34 as additional partners of p45 SKP2 in vivo . CUL‐1 also associates with cyclin A and p19 SKP1 in vivo and, with p45 SKP2 , they assemble into a large multiprotein complex. In Saccharomyces cerevisiae , a complex of similar molecular composition (an F‐box protein, a member of the cullin family and a homolog of p19 SKP1 ) forms a functional E3 ubiquitin protein ligase complex, designated SCF CDC4 , that facilitates ubiquitination of a CDK inhibitor by CDC34. The data presented here imply that the p45 SKP2 –CUL‐1–p19 SKP1 complex may be a human representative of an SCF‐type E3 ubiquitin protein ligase. We propose that all eukaryotic cells may use a common ubiquitin conjugation apparatus to promote S phase. Finally, we show that multiprotein complex formation involving p45 SKP2 –CUL‐1 and p19 SKP1 is governed, in part, by periodic, S phase‐specific accumulation of the p45 SKP2 subunit and by the p45 SKP2 ‐bound cyclin A–CDK2. The dependency of p45 SKP2 –p19 SKP1 complex formation on cyclin A–CDK2 may ensure tight coordination of the activities of the cell cycle clock with those of a potential ubiquitin conjugation pathway.