Cyclin F is degraded during G2-M by mechanisms fundamentally different from other cyclins.
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 G(2)/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.
Fung
Tsz Kan
TK
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Siu
Wai Yi
WY
Yam
Cain H
CH
Lau
Anita
A
Poon
Randy Y C
RY
D002460:Cell Line; D016213:Cyclins / Q000378:metabolism*; D004249:DNA Damage; D016195:G2 Phase; D006801:Humans; D006868:Hydrolysis; D008938:Mitosis; D011994:Recombinant Proteins / Q000378:metabolism; D016196:S Phase
C503669:CCNF protein, human; D016213:Cyclins; D011994:Recombinant Proteins