Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC

被引:147
作者
Ayad, NG
Rankin, S
Murakami, M
Jebanathirajah, J
Gygi, S
Kirschner, MW
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA
[3] NCI, Frederick, MD 21702 USA
关键词
D O I
10.1016/S0092-8674(03)00232-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Entry into mitosis requires the activation of cdk1/ cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cclk1/cyclin B activity and thus mitotic entry and exit.
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页码:101 / 113
页数:13
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