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 promoti ng factor (MPF), a complex composed of cdc2 and a B-type cyclin, Cyclin B1 nuclear localization involves phosphorylation within a region called the cy toplasmic retention signal, which also contains a nuclear export signal. Th e mechanism of MPF nuclear localization remains unclear since it contains n o functional nuclear localization signal (NLS). We exploited the yeast two- hybrid screen to find protein(s) potentially mediating localization of cycl in 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 histo ne H1 kinase activity. Cyclin B1 and cyclin F also colocalize through immun ofluorescence studies. Additionally, deletion analysis revealed that each p utative NLS of cyclin F is functional. Taken together, the data suggest tha t the NLS regions of cyclin F regulate cyclin B1 localization to the nucleu s. The interaction between cyclin B1 and cyclin F represents the first exam ple of direct cyclin-cyclin binding, and elucidates a novel mechanism that regulates MPF localization and function.