Aurora A Regulates Prometaphase Progression by Inhibiting the Ability of RASSF1A to Suppress APC-Cdc20 Activity

Song, Su Jung; Song, Min Sup; Kim, Soon Jung; Kim, So Yeon; Kwon, Soon-Jung; Kim, Jhin Gook; Calvisi, Diego F.; Kang, Dongmin; Lim, Dae–Sik

doi:10.1158/0008-5472.can-08-3984

Cited by 47 publications

(46 citation statements)

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“…Furthermore, it has been reported that RASSF1A overexpression induces a G2/M cell cycle arrest [113], most likely by RASSF1A regulating APC-Cdc20 E3 ligase activity which affects mitotic progression [114]. In addition, it was found that Aurora A regulates RASSF1A during prometaphase progression [115,116], while Aurora B phosphorylation of RASSF1A plays a role in the regulation of cytokinesis [117]. These reports strongly suggest that RASSF1A has diverse roles in mitosis.…”

Section: Mammalian Hippo Signalling In the G2/m Phase Of The Cell Cyclementioning

confidence: 92%

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hergovich

Hemmings

2012

Seminars in Cell & Developmental Biology

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Over the past decade Hippo kinase signalling has been established as an essential tumour suppressor pathway controlling tissue growth in flies and mammals. All members of the Hippo core signalling cassette are conserved from yeast to humans, whereby the yeast analogues of Hippo, Mats and Lats are central components of the mitotic exit network and septation initiation network in budding and fission yeast, respectively. Here, we discuss how far core Hippo signalling components in Drosophila melanogaster and mammals have reported similar mitotic functions as already established for their highly conserved yeast counterparts.

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Section: Mammalian Hippo Signalling In the G2/m Phase Of The Cell Cyclementioning

confidence: 92%

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hergovich

Hemmings

2012

Seminars in Cell & Developmental Biology

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“…Upon phosphorylation by Aurora A, RASSF1A fails to interact with Cdc20 thereby relieving APC inhibition, leading to degradation of cyclins and mitotic progression [29]. Interestingly, RABP1/MAP1S was recently shown to enhance autophagy by suppressing genomic instability and tumorigenesis [30].…”

Section: Kdamentioning

confidence: 99%

RASSF tumor suppressor gene family: Biological functions and regulation

et al. 2014

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a b s t r a c tGenetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFjB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

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“…RASSF1A is phosphorylated by both Aurora A and Aurora B (10,11), and phosphorylation of RASSF1A by Aurora A prevents RASSF1A from exerting its inhibitory function on APC-Cdc20 (11). The role of phosphorylation of RASSF1A by Aurora B, which has remained unknown, is addressed here.…”

Section: Introductionmentioning

confidence: 98%

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

Song¹,

Kim²,

Song³

et al. 2009

Cancer Research

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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 microtubule 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 RASS-F1A toward anaphase-promoting complex-Cdc20. However, the role of Aurora B-mediated RASSF1A phosphorylation remains unknown. Here, we show that phosphorylation of RASS-F1A 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 Syntaxin16 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]

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Aurora A Regulates Prometaphase Progression by Inhibiting the Ability of RASSF1A to Suppress APC-Cdc20 Activity

Cited by 47 publications

References 50 publications

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

RASSF tumor suppressor gene family: Biological functions and regulation

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

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