WT1 interacts with MAD2 and regulates mitotic checkpoint function

Shandilya, Jayasha, Toska, Eneda, & Richard, Derek J. (2014) WT1 interacts with MAD2 and regulates mitotic checkpoint function. Nature Communications, 5(4903), pp. 1-9.

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Tumour suppressors safeguard the fidelity of the mitotic checkpoint by transcriptional regulation of genes that encode components of the mitotic checkpoint complex (MCC). Here we report a new role for the tumour suppressor and transcription factor, WT1, in the mitotic checkpoint. We show that WT1 regulates the MCC by directly interacting with the spindle assembly checkpoint protein, MAD2. WT1 colocalizes with MAD2 during mitosis and preferentially binds to the functionally active, closed-conformer, C-MAD2. Furthermore, WT1 associates with the MCC containing MAD2, BUBR1 and CDC20, resulting in prolonged inhibition of the anaphase-promoting complex/cyclosome (APC/C) and delayed degradation of its substrates SECURIN and CYCLIN B1. Strikingly, RNA interference-mediated depletion of WT1 leads to enhanced turnover of SECURIN, decreased lag time to anaphase and defects in chromosome segregation. Our findings identify WT1 as a regulator of the mitotic checkpoint and chromosomal stability.

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3 citations in Scopus
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2 citations in Web of Science®

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15 since deposited on 12 Jun 2015
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ID Code: 84738
Item Type: Journal Article
Refereed: No
DOI: 10.1038/ncomms5903
ISSN: 2041-1723
Subjects: Australian and New Zealand Standard Research Classification
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: 2014 Macmillan Publishers Limited
Deposited On: 12 Jun 2015 01:40
Last Modified: 15 Jun 2015 20:57

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