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J. Biol. Chem., Vol. 277, Issue 38, 35140-35149, September 20, 2002
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From the Department of Biochemistry, Hong Kong University of
Science and Technology, Clear Water Bay, Hong Kong
Cyclin F, a cyclin that can form SCF complexes
and bind to cyclin B, oscillates in the cell cycle with a pattern
similar to cyclin A and cyclin B. Ectopic expression of cyclin F
arrests the cell cycle in G2/M. How the level of
cyclin F is regulated during the cell cycle is completely obscure. Here
we show that, similar to cyclin A, cyclin F is degraded when the
spindle assembly checkpoint is activated and accumulates when the DNA
damage checkpoint is activated. Cyclin F is a very unstable protein
throughout much of the cell cycle. Unlike other cyclins, degradation of
cyclin F is independent of ubiquitination and proteasome-mediated
pathways. Interestingly, proteolysis of cyclin F is likely to involve
metalloproteases. Rapid destruction of cyclin F does not require
the N-terminal F-box motif but requires the COOH-terminal PEST
sequences. The PEST region alone is sufficient to interfere with the
degradation of cyclin F and confer instability when fused to cyclin A. These data show that although cyclin F is degraded at similar time as the mitotic cyclins, the underlying mechanisms are entirely distinct.
Cyclin F Is Degraded during G2-M by Mechanisms
Fundamentally Different from Other Cyclins*
,
*
This work was supported in part by awards and grants from
the Croucher Foundation, the Philip Morris External Research Program, and Research Grants Council Grant HKUST6194/99 M (to R. Y. C. P.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Division of Biology, MC 156-29, California
Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125.
§
To whom correspondence should be addressed: Dept. of Biochemistry,
Hong Kong University of Science and Technology, Clear Water Bay, Hong
Kong. Tel.: 852-23588718; Fax: 852-23581552; E-mail: bcrandy@ust.hk.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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