Without Cks1 (filled squares), CDC20 expression is flat.


For perhaps a decade, Suc1 was the hardy little protein that featured in almost every cell cycle paper. But it was used only as a reagent—its binding to cyclin-dependent kinases (such as Cdc2 or Cdc28) yielded nearly pure MPF.

Then the budding yeast version, called Cks1, was found to be essential for growth. Now, May Morris, Steven Reed, and colleagues (The Scripps Research Institute, La Jolla, CA) have found that Cks1 helps shuffle proteins, including Cdc28, at the critical CDC20 cell cycle promoter, thus helping push cells through mitosis.

Cdc20 activates the ubiquitination machinery, which then destroys mitotic cyclins and sister chromatid glue to initiate anaphase. Morris stumbled on CDC20 because its overexpression suppressed a cks1 mutant. She then found that Cks1 helped turn on CDC20 expression during mitosis, and that Cks1 and Cdc28 both localized to the CDC20 promoter. But a version of Cdc28 that interacts poorly with Cks1 actually stuck to the promoter more avidly, suggesting that Cdc28 binds the promoter first, then brings in Cks1, and finally is kicked off via a Cks1-related mechanism.

Indeed, at the peak of both CDC20 expression and Cks1 binding to the promoter, Cdc28 was released. The release may be triggered by the proteasome, which cofractionates with Cks1 and can also bind transiently to the CDC20 promoter. Proteasome protease function is not necessary for CDC20 expression, so perhaps the proteasome is recycling a promoter-bound protein, such as Cdc28, after it has fulfilled some essential phosphorylation function, or remodeling either chromatin or a stalled transcription complex. ▪


Morris, M.C., et al.