Mitotic entry: A matter of oscillating destruction

Entry into mitosis is essentially driven by cyclin B1 and its associated catalytically active partner Cdk1. While cyclin B1 is kept cytoplasmic throughout interphase, nuclear accumulation occurs just prior to mitosis. This restriction is thought to be part of an oscillating mechanism to properly time mitotic entry. A novel nuclear SCF-type mammalian E3 ligase defined by the F-box containing protein NIPA (nuclear interaction partner of ALK), SCF ^NIPA, targets nuclear cyclin B1 in interphase while it allows for accumulation at G₂/M. Thus, oscillating ubiquitination of nuclear cyclin B1 driven by the SCF^NIPA complex contributes to the timing of mitotic entry in the mammalian cell cycle.