Human cyclin F.
Cyclins are important regulators of cell cycle transitions through their ability to bind and activate cyclin-dependent protein kinases. In mammals several classes of cyclins exist which are thought to co-ordinate the timing of different events necessary for cell cycle progression. Here we describe the identification of a novel human cyclin, cyclin F, isolated as a suppressor of the G1/S deficiency of a Saccharomyces cerevisiae cdc4 mutant. Cyclin F is the largest cyclin, with a molecular weight of 87 kDa, and migrates as a 100-110 kDa protein. It contains an extensive PEST-rich C-terminus and a cyclin box region that is most closely related to cyclins A and B. Cyclin F mRNA is ubiquitiously expressed in human tissues. It fluctuates dramatically through the cell cycle, peaking in G2 like cyclin A and decreasing prior to decline of cyclin B mRNA. Cyclin F protein accumulates in interphase and is destroyed at mitosis at a time distinct from cyclin B. Cyclin F shows regulated subcellular localization, being localized in the nucleus in most cells, with a significant percentage of cells displaying only perinuclear staining. Overexpression of cyclin F, or a mutant lacking the PEST region, in human cells resulted in a significant increase in the G2 population, implicating cyclin F in the regulation of cell cycle transitions. The ubiquitous expression and phylogentic conservation of cyclin F suggests that it is likely to coordinate essential cell cycle events distinct from those regulated by other cyclins.
Bai
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Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030.
Richman
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Elledge
S J
SJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D019926:Cyclin B; D016213:Cyclins / Q000096:biosynthesis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D044767:Ubiquitin-Protein Ligases; D015003:Yeasts / Q000235:genetics
C503669:CCNF protein, human; C091274:CLB4 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D016213:Cyclins; D018076:DNA, Complementary; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D005656:Fungal Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases