Abstract 4970: Complex regulation of RIP140 gene expression by E2F transcription factors

Abstract

Abstract We recently showed that RIP140 (Receptor Interacting protein of 140 kDa), a regulator of nuclear receptor activity, was involved in the control of cell proliferation and able to repress E2F1 activity. We now demonstrate that RIP140 and E2F1 comprise a novel transcriptional regulatory loop. We first observed that RIP140 mRNA levels increased during the G1/S and G2/M transitions and were reduced in tissues from E2F1 null mice. Furthermore, we identified the RIP140 gene as a transcriptional target of E2F1, showing, by transient transfection, that overexpression of E2F1/DP1 strongly increased transcription of the RIP140 promoter. Bioinformatic analysis identified several binding sites for E2Fs in the proximal promoter region and we evidenced the direct binding of E2F1/DP1 on these sequences by gel shift analysis. However, site directed mutagenesis of these elements only modestly affected transactivation of the RIP140 promoter by E2F1/DP1, thus suggesting an indirect recruitment of E2Fs on the promoter. This was strengthened by the observation that overexpression of E2F1, 2 or 3 alone was very potent in increasing transcription from the RIP140 promoter. Moreover, overexpression of DP1 produced a negative effect on this regulation which was also strongly repressed by RIP140 itself. Altogether, these results revealed a complex control loop between E2Fs and RIP140 and the molecular mechanisms underlying these atypical regulations are currently under investigation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4970.