Tumor suppressor SMAR1 activates and stabilizes p53 through its arginine-serine-rich motif

Jalota, Archana ; Singh, Kamini ; Pavithra, Lakshminarasimhan ; Kaul-Ghanekar, Ruchika ; Jameel, Shahid ; Chattopadhyay, Samit (2005) Tumor suppressor SMAR1 activates and stabilizes p53 through its arginine-serine-rich motif The Journal of Biological Chemistry, 280 (16). pp. 16019-16029. ISSN 0021-9258

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Official URL: http://www.jbc.org/content/280/16/16019.short

Related URL: http://dx.doi.org/10.1074/jbc.M413200200


Various stresses and DNA-damaging agents trigger transcriptional activity of p53 by post-translational modifications, making it a global regulatory switch that controls cell proliferation and apoptosis. Earlier we have shown that the novel MAR-associated protein SMAR1 interacts with p53. Here we delineate the minimal domain of SMAR1 (the arginine-serine-rich domain) that is phosphorylated by protein kinase C family proteins and is responsible for p53 interaction, activation, and stabilization within the nucleus. SMAR1-mediated stabilization of p53 is brought about by inhibiting Mdm2-mediated degradation of p53. We also demonstrate that this arginine-serine (RS)-rich domain triggers the various cell cycle modulating proteins that decide cell fate. Furthermore, phenotypic knock-down experiments using small interfering RNA showed that SMAR1 is required for activation and nuclear retention of p53. The level of phosphorylated p53 was significantly increased in the thymus of SMAR1 transgenic mice, showing in vivo significance of SMAR1 expression. This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the "guardian of the genome."

Item Type:Article
Source:Copyright of this article belongs to The American Society for Biochemistry and Molecular Biology.
ID Code:60238
Deposited On:08 Sep 2011 09:32
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