Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20

Michal Shteinberg, Yana Protopopov, Tamar Listovsky, Michael Brandeis, Avram Hershko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


Exit from mitosis in eukaryotic cells is regulated by the cyclosome (also called anaphase promoting complex or APC), a multisubunit ubiquitin ligase that acts on mitotic cyclins. Previous studies in a cell-free system from clam oocytes have shown that the activation of the cyclosome at the end of mitosis involves its phosphorylation by protein kinase Cdk1/cyclin B. Genetic and biochemical studies have furthermore indicated that cyclosome activity also requires a WD-40 repeat containing protein called Fizzy (FZY) or Cdc20. It has been suggested that in the presence of FZY, the phosphorylation of the cyclosome is not critical for its activation. By contrast, we find that the activity of the interphase, non-phosphorylated form of the cyclosome from clam embryos is not stimulated by FZY to a significant extent. However, when interphase cyclosome is first incubated with protein kinase Cdk1/cyclin B, the subsequent supplementation of FZY greatly stimulates its cyclin-ubiquitin ligase activity. Furthermore, phosphatase treatment of purified mitotic cyclosome prevents its stimulation by FZY, a process that can be reversed by the action of protein kinase Cdk1/cyclin B. We conclude that in the early embryonic cell cycles, the primary event in the activation of the cyclosome at the end of mitosis is its Cdk1-dependent phosphorylation and activation by FZY takes place in a subsequent process.

Original languageAmerican English
Pages (from-to)193-198
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 24 Jun 1999

Bibliographical note

Funding Information:
We thank Dvorah Ganoth for participating in the initial phases of this study, and Julian Gannon for the anti-Cdc27 antibody. This work was supported by a United States-Israel Binational Science Foundation grant to A.H., and by the Israel Science Foundation and the Horovitz Foundation to MB.


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