Cyclin A/cdk2 regulated adenomatous polyposis coli-dependent mitotic spindle anchoring

Beamish, Heather, de Boer, Leonore, Giles, Nicole, Stevens, Frankie, Oakes, Vanessa, & Gabrielli, Brian (2009) Cyclin A/cdk2 regulated adenomatous polyposis coli-dependent mitotic spindle anchoring. Journal of Biological Chemistry, 284(42), pp. 29015-29023.

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Abstract

Mutations in adenomatous polyposis coli (APC) protein is a major contributor to tumor initiation and progression in several tumor types. These mutations affect APC function in the Wnt-β-catenin signaling and influence mitotic spindle anchoring to the cell cortex and orientation. Here we report that the mitotic anchoring and orientation function of APC is regulated by cyclin A/cdk2. Knockdown of cyclin A and inhibition of cdk2 resulted in cells arrested in mitosis with activation of the spindle assembly checkpoint. The mitotic spindle was unable to form stable attachments to the cell cortex, and this resulted in the spindles failing to locate to the central position in the cells and undergo dramatic rotation. We have demonstrated that cyclin A/cdk2 specifically associates with APC in late G2 phase and phosphorylates it at Ser-1360, located in the mutation cluster region of APC. Mutation of APC Ser-1360 to Ala results in identical off-centered mitotic spindles. Thus, this cyclin A/cdk2-dependent phosphorylation of APC affects astral microtubule attachment to the cortical surface in mitosis.

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13 citations in Scopus
7 citations in Web of Science®
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ID Code: 43162
Item Type: Journal Article
Refereed: Yes
Additional Information: This research was originally published in the Journal of Biological Chemistry. Heather Beamish, Leonore de Boer, Nichole Giles, Frankie Stevens, Vanessa Oakes and Brian Gabrielli. Cyclin A/cdk2 Regulates Adenomatous Polyposis Coli-dependent Mitotic Spindle Anchoring. Journal of Biological Chemistry. 2009; 284:29015-29023. © the American Society for Biochemistry and Molecular Biology.
Keywords: Cyclin A, Mitosis, Adenomatous Polyposis Coli, Spindle Anchoring, Cell Cyle
DOI: 10.1074/jbc.M109.042820
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 13 Jul 2011 13:10
Last Modified: 13 Jul 2017 12:02

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