Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction.
The key regulator of G(2)-M transition of the cell cycle is M-phase promoting factor (MPF), a complex composed of cdc2 and a B-type cyclin. Cyclin B1 nuclear localization involves phosphorylation within a region called the cytoplasmic retention signal, which also contains a nuclear export signal. The mechanism of MPF nuclear localization remains unclear since it contains no functional nuclear localization signal (NLS). We exploited the yeast two-hybrid screen to find protein(s) potentially mediating localization of cyclin B1 and identified a novel interaction between cyclin B1 and cyclin F. We found that cdc2, cyclin B1 and cyclin F form a complex that exhibits histone H1 kinase activity. Cyclin B1 and cyclin F also colocalize through immunofluorescence studies. Additionally, deletion analysis revealed that each putative NLS of cyclin F is functional. Taken together, the data suggest that the NLS regions of cyclin F regulate cyclin B1 localization to the nucleus. The interaction between cyclin B1 and cyclin F represents the first example of direct cyclin-cyclin binding, and elucidates a novel mechanism that regulates MPF localization and function.
Kong
M
M
Department of Chemistry, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093-0367, USA.
Barnes
E A
EA
Ollendorff
V
V
Donoghue
D J
DJ
D000818:Animals; D001692:Biological Transport; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D019926:Cyclin B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D016213:Cyclins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008540:Meiosis / Q000235:genetics; D008954:Models, Biological; D019814:Myristic Acid / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D020798:Two-Hybrid System Techniques; D014982:Xenopus laevis / Q000235:genetics
C534699:CCNB1 protein, human; C503669:CCNF protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D019913:Nuclear Localization Signals; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019814:Myristic Acid; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase