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Regulation of the Bub2/Bfal GAP complex by Cdc5 and cell cycle checkpoints
Author(s): Hu FH, Wang YC, Liu D, Li YM, Qin J, Elledge SJ
Source: CELL    Volume: 107    Issue: 5    Pages: 655-665    Published: NOV 30 2001  
Times Cited: 118     References: 41     
Abstract: During mitosis, a ras-related GTPase (Tem1) binds GTP and activates a signal transduction pathway to allow mitotic exit. During most of the cell cycle, Tem1 function is antagonized by a GTPase-activating protein complex, Bfa1/Bub2. How the Bfa1/Bub2 complex is regulated is not well understood. We find that Polo/ Cdc5 kinase acts upstream of Bfa1/Bub2 in the mitotic exit network. Cdc5 phosphorylates Bfa1 and acts to antagonize Bfa1 function to promote mitotic exit. Bfa1 is regulated by multiple cell cycle checkpoints. The spindle assembly and spindle orientation checkpoints inhibit Bfa1 phosphorylation. DNA damage does not inhibit Bfa1 phosphorylation and instead causes: a Rad53- and Dun1-dependent modification of Bfa1. Regulation of Bfa1 may therefore be a key step controlled by multiple checkpoint pathways to ensure a mitotic arrest.
Document Type: Article
Language: English
Reprint Address: Elledge, SJ (reprint author), Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA
Addresses:
1. Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA
2. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA
Publisher: CELL PRESS, 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA
Subject Category: Biochemistry & Molecular Biology; Cell Biology
IDS Number: 499MQ
ISSN: 0092-8674
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