Cdk1 is essential for mammalian cyclosome/APC regulation

Tamar Listovsky, Amit Zor, Ayelet Laronne, Michael Brandeis

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The cyclosome/APC (anaphase-promoting complex), the major component of cell-cycle-specific ubiquitin-mediated proteolysis of mitotic cyclins and of other cell cycle proteins, is essential for sister chromatid separation and for exit from mitosis. Cyclosome activity and substrate specificity are modulated by phosphorylation and by transient interactions with Fizzy/cdc20 (Fzy) and Fizzy-related/Hct1/Cdh1 (Fzr). This regulation has been studied so far in Drosophila embryos, in yeast, and in cell-free extracts in vitro. Studying cyclosome regulation in mammalian cells in vivo we found that both Fzr overexpression and Cdk1 inhibition can override the prometaphase checkpoint. We further show that Fzr activation of the cyclosome is negatively regulated by Cdk1. Finally, we show that the mammalian cdc14 phosphatase, like its budding yeast homologue, plays a role in cyclosome pathway regulation. These results suggest that Cdk1 is essential for coupling various activities of the cyclosome and in particular for preventing Fzr from short-circuiting the spindle pole checkpoint. Cdk1-cyclin B is thus an inhibitor, activator, and substrate of the cyclosome. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
JournalExperimental Cell Research
Volume255
Issue number2
DOIs
StatePublished - 15 Mar 2000
Externally publishedYes

Bibliographical note

Funding Information:
We thank C. Lehner, J. Gannon, and P. Hieter for antibodies; E. Harlow, S. Geley, R. Graeser, C. Hill, L. Li, and J. E. Dixon for plasmids; and Y. Gruenbaum and A. Hershko for discussions. This work was funded by the Israel Science Foundation and the Horovitz Foundation.

Funding

We thank C. Lehner, J. Gannon, and P. Hieter for antibodies; E. Harlow, S. Geley, R. Graeser, C. Hill, L. Li, and J. E. Dixon for plasmids; and Y. Gruenbaum and A. Hershko for discussions. This work was funded by the Israel Science Foundation and the Horovitz Foundation.

FundersFunder number
Horovitz Foundation
Israel Science Foundation

    Keywords

    • Cdc20
    • Cyclin B
    • Fizzy
    • Fizzy-related
    • Hct1
    • cdc14

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