EMBO Fellows Meeting 2012
EMBO Fellows Meeting 2012
EMBO Fellows Meeting 2012
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Tamar Listovsky<br />
<strong>EMBO</strong> <strong>Fellows</strong> <strong>Meeting</strong> <strong>2012</strong><br />
Sequestration of CDH1 by REV7/Mad2B during prometaphase prevents premature<br />
APC/C activation<br />
Abstract<br />
Regulation of the activity of the anaphase promoting complex/cyclosome (APC/C) is crucial for orderly<br />
progression through mitosis and accurate chromosome segregation. This requires that the APC/C is inhibited<br />
during metaphase and that it is correctly activated at the onset of anaphase, first by CDC20 and then by CDH1.<br />
The regulation of the switch between APC/C Cdc20 and APC/C Cdh1 is still no well understood, but is dependent on<br />
dephosphorylation of both the APC/C and CDH1. We have show that the APC/C Cdh1 inhibitor MAD2B/REV7<br />
sequesters CDH1 away from the APC/C during metaphase helping prevent it from activating the APC/C<br />
prematurely. At the onset of anaphase, MAD2B/REV7 is rapidly destroyed by APC/C Cdc20, releasing CDH1 to<br />
activate the dephosphorylated APC/C. In the absence of MAD2B/REV7, premature activation of the APC/C Cdh1<br />
leads to deregulation of key substrates of APC/C Cdh1 , notably the Aurora A and B kinases. In turn, this is<br />
associated with loss of coordination of the metaphase to anaphase transition and frequent mitotic aberrations.<br />
Thus, in vertebrates sequestration of CDH1 by MAD2B provides an important parallel mechanism to CDH1<br />
phosphorylation for preventing premature activation of APC/C Cdh1 .<br />
Tamar Listovsky and Julian E. Sale<br />
Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Hills Road,<br />
Cambridge, CB2 0QH, UK<br />
14-17 June <strong>2012</strong>, Heidelberg, Germany
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