Aurora B-Mediated Phosphorylation of RASSF1A Maintains Proper Cytokinesis by Recruiting Syntaxin16 to the Midzone and Midbody

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Aurora B is critically involved in ensuring proper cytokinesis and maintaining genomic stability. The tumor suppressor RASSF1A regulates cell cycle progression by regulating mitotic progression, G(1)-S transition, and microtubute stability. We previously reported that both Aurora A and Aurora B phosphorylate RASSF1A, and showed that phosphorylation of RASSF1A by Aurora A blocks the inhibitory function of RASSF1A toward anaphase-promoting complex-Cdc20. However, the role of Aurora B-mediated RASSF1A phosphorylation remains unknown. Here, we show that phosphorylation of RASSF1A on Ser203 by Aurora B during late mitosis has a critical role in regulating cytokinesis. Notably, RASSF1A interacts with Syntaxin16, a member of the t-SNARE family at the midzone and midbody during late mitosis. Aurora B is required for this interaction and for the subsequent recruitment of Syntaxin16 to the midzone and midbody, a prerequisite for the successful completion of cytokinesis. Furthermore, Aurora B depletion results in a failure of Syntaxin16 to properly localize to the midzone and midbody, a mislocalization that was prevented by overexpression of the phosphomimetic RASSF1A (S203D) mutant. Finally, either depletion of Syntaxin]6 or expression of the nonphosphorylatable RASSF1A (S203A) mutant results in cytokinesis defects. Our findings implicate Aurora B-mediated phosphorylation of RASSF1A in the regulation of cytokinesis. [Cancer Res 2009;69(22):8540-4]
Publisher
AMER ASSOC CANCER RESEARCH
Issue Date
2009-11
Language
English
Article Type
Article
Keywords

PROGRESSION; POLES; CELLS

Citation

CANCER RESEARCH, v.69, no.22, pp.8540 - 8544

ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-09-1554
URI
http://hdl.handle.net/10203/16499
Appears in Collection
BS-Journal Papers(저널논문)
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