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J Biol Chem. 2011 Feb 25;286(8):6253-61. doi: 10.1074/jbc.M110.178210. Epub 2011 Jan 3.

The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2.

Author information

1
Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, California 91010, USA.

Abstract

The RASSF1A tumor suppressor protein interacts with the pro-apoptotic mammalian STE20-like kinases MST1 and MST2 and induces their autophosphorylation and activation, but the mechanism of how RASSF1A activates MST1/2 is unclear. Okadaic acid treatment and PP2A knockdown promoted MST1/2 phosphorylation. Data from dephosphorylation assays and reduced activation of MST1/2 seen after RASSF1A depletion suggest that dephosphorylation of MST1/2 on Thr-183 and Thr-180 by PP2A is prevented by RASSF1A, shifting the balance of MST1/2 to the activated autophosphorylated form. In addition to preventing dephosphorylation, RASSF1A also stabilized the MST2 protein. Through binding to MST1/2, RASSF1A supports maintenance of MST1/2 phosphorylation, promoting an active state of the MST kinases and favoring induction of apoptosis. This is one of the first examples of a tumor suppressor acting as an inhibitor of a specific dephosphorylation pathway.

PMID:
21199877
PMCID:
PMC3057778
DOI:
10.1074/jbc.M110.178210
[Indexed for MEDLINE]
Free PMC Article

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