Role of the Tumor Suppressor RASSF1A in Mst1-Mediated Apoptosis

American Association for Cancer Research (AACR) - Tập 66 Số 5 - Trang 2562-2569 - 2006
Hyun Jung Oh1, Kyung-Kwon Lee2, Su Jung Song1, Mi Sun Jin3, Min Sup Song1,4, Joo‐Hyeon Lee1, Chang Rak Im1, Jie‐Oh Lee3, Shin Yonehara2, Dae‐Sik Lim1,5
11Department of Biological Sciences, Biomedical Research Center;
23Graduate School of Biostudies, Kyoto University, Kyoto, Japan
32Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, South Korea; and
4Molecular & Cellular Oncology
5Korea Advanced Institute of Science and Technology

Tóm tắt

AbstractMammalian sterile 20–like kinase 1 (Mst1) is activated by both caspase-mediated cleavage and phosphorylation in response to apoptotic stimuli, including Fas ligation. Here, we examined the possible role of the tumor suppressor RASSF1A in Mst1 activation and Mst1-mediated apoptosis induced by death receptor signaling. Immunoprecipitation and immunofluorescence analyses revealed that Mst1 was associated with RASSF1A in cultured mammalian cells, with both proteins colocalizing to microtubules throughout the cell cycle. Whereas purified recombinant RASSF1A inhibited the kinase activity of purified recombinant Mst1 in vitro, overexpression of RASSF1A increased the kinase activity of Mst1 in intact cells, suggesting that regulation of Mst1 by RASSF1A in vivo involves more than the simple association of the two proteins. Both the activation of Mst1 and the incidence of apoptosis induced by Fas ligation were markedly reduced in cells depleted of RASSF1A by RNA interference and were increased by restoration of RASSF1A expression in RASSF1A-deficient cells. Moreover, the stimulatory effect of RASSF1A overexpression on Fas-induced apoptosis was inhibited by depletion of Mst1. These findings indicate that RASSF1A facilitates Mst1 activation and thereby promotes apoptosis induced by death receptor signaling. (Cancer Res 2006; 66(5): 2562-9)

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American Association for Cancer Research (AACR)

Tập 66 Số 5

2562-2569

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