Abstract 3151: Posttranscriptional regulation of p21 by MCG10, an RNA-binding protein and a target of tumor suppressor p53

Abstract

Abstract The tumor suppressor p53 plays a crucial role in regulating many cellular processes, such as cell cycle arrest, apoptosis, senescence and cell metabolism, in response to stress signals. As a transcription factor, p53 modulates the expression of a plethora of genes, including p21, Killer/DR5, GADD45, TIGAR and MDM2. The tumor suppressor function of p53 is further underscored by the high propensity of p53 mutations found in human cancer. RNA-binding proteins are key modulators in RNA metabolism involved in alternative splicing, mRNA stability, mRNA transport as well as translation. Abnormal expression of RNA-binding proteins is implicated in a growing number of human diseases ranging from neurological disorders to cancer. Here, we showed that MCG10, an RNA-binding protein and a target of p53, regulates the stability of cell cycle inhibitor p21 transcript. Indeed, we found that MCG10 decreases p21 levels induced upon DNA damage. In addition, we showed that MCG10 directly binds to the 3′untranslated region of p21 transcript to destabilize it. Furthermore, we generated MCF7 breast adenocarcinoma and RKO colon carcinoma cell lines in which MCG10 is inducibly knocked down. We found that MCG10 is required for cell proliferation. In addition, we showed that deficiency in MCG10 leads to an increase in basal and DNA damage-induced p21 levels. Taken together, we uncovered a role for RNA-binding protein MCG10 in modulating the p53 pathway through posttranscriptional regulation of p21. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3151.