XB-ART-5185Dev Cell. June 1, 2003; 4 (6): 813-26.
Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase.
Progression through mitosis occurs because cyclin B/Cdc2 activation induces the anaphase promoting complex (APC) to cause cyclin B destruction and mitotic exit. To ensure that cyclin B/Cdc2 does not prematurely activate the APC in early mitosis, there must be a mechanism delaying APC activation. Emi1 is a protein capable of inhibiting the APC in S and G2. We show here that Emi1 is phosphorylated by Cdc2, and on a DSGxxS consensus site, is subsequently recognized by the SCF(betaTrCP/Slimb) ubiquitin ligase and destroyed, thus providing a delay for APC activation. Failure of betaTrCP-dependent Emi1 destruction stabilizes APC substrates and results in mitotic catastrophe including centrosome overduplication, potentially explaining mitotic deficiencies in Drosophila Slimb/betaTrCP mutants. We hypothesize that Emi1 destruction relieves a late prophase checkpoint for APC activation.
PubMed ID: 12791267
Article link: Dev Cell.
Grant support: CA09302 NCI NIH HHS , CA09302 NCI NIH HHS , CA09302 NCI NIH HHS , CA09302 NCI NIH HHS , CA09302 NCI NIH HHS , CA09302 NCI NIH HHS , GM07365 NIGMS NIH HHS , GM54811 NIGMS NIH HHS , GM60439 NIGMS NIH HHS
Genes referenced: btrc ccnb1.2 cdk1 fbxo5 pold1