TY - JOUR
T1 - Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC
AU - Ayad, Nagi G.
AU - Rankin, Susannah
AU - Murakami, Monica
AU - Jebanathirajah, Judith
AU - Gygi, Steven
AU - Kirschner, Marc W.
N1 - Funding Information:
We thank Cathie Pfleger for the design and initial implementation of the Cdh1 substrate screen. We would like to thank Teresita Bernal for technical assistance with the Cdh1 screen. We would like to thank all members of the Kirschner lab for helpful discussions, especially Olaf Stemmann, Yong Wan, Hui Zhou, Sharon Eden, and Jeffrey Peterson. We would like to thank Hanno Steen for helpful discussions regarding quantification of wee1 phosphorylation. We would like to thank John Rush and Cell Signaling Technology for the gift of the phosphorylated and nonphosphorylated wee1 peptides. We would also like to thank members of the McKeon laboratory for helpful discussions and the production of the anti-mouse-Tome-1 antibody. S.G. was supported by NIH grant HG00041. N.G.A. is a fellow of the Leukemia and Lymphoma society.
PY - 2003/4/4
Y1 - 2003/4/4
N2 - 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 cdk1/cyclin B activity and thus mitotic entry and exit.
AB - 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 cdk1/cyclin B activity and thus mitotic entry and exit.
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U2 - 10.1016/S0092-8674(03)00232-0
DO - 10.1016/S0092-8674(03)00232-0
M3 - Article
C2 - 12679038
AN - SCOPUS:0037418836
VL - 113
SP - 101
EP - 113
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1
ER -