Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase

Shirly Lahav-Baratz, Valery Sudakin, Joan V. Ruderman, Avram Hershko

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


Cyclin B/cdc2 is responsible both for driving cells into mitosis and for activating the ubiquitin-dependent degradation of mitotic cyclins near the end of mitosis, an event required for the completion of mitosis and entry into interphase of the next cell cycle. Previous work with cell-free extracts of rapidly dividing clam embryos has identified two specific components required for the ubiquitination of mitotic cyclins: E2-C, a cyclin-selective ubiquitin carrier protein that is constitutively active during the cell cycle, and E3-C, a cyclin-selective ubiquitin ligase that purifies as part of a ≃1500-kDa complex, termed the cyclosome, and which is active only near the end of mitosis. Here, we have separated the cyclosome from its ultimate upstream activator, cdc2. The mitotic, active form of the cyclosome can be inactivated by incubation with a partially purified, endogenous okadaic acid- sensitive phosphatase; addition of cdc2 restores activity to the cyclosome after a lag that reproduces that seen previously in intact cells and in crude extracts. These results demonstrate that activity of cyclin-ubiquitin ligase is controlled by reversible phosphorylation of the cyclosome complex.

Original languageEnglish (US)
Pages (from-to)9303-9307
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - Sep 26 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


  • cell cycle
  • cyclin degradation
  • mitosis


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