Ribosomal proteins play an important role in p53 activation in response to ribosomal stress. Multiple ribosomal proteins, including L5, L11, L23, and S7, have been shown to bind and inhibit MDM2, leading to p53 activation. However, it is not known whether ribosomal protein inhibition of MDM2 is specific to certain, but not all, ribosomal proteins. Here, we show that L29 and L30, two ribosomal proteins from the large ribosome subunit, do not bind to MDM2 and do not inhibit MDM2-mediated p53 suppression, indicating that the ribosomal protein regulation of the MDM2-p53 feedback loop is specific. Interestingly, direct perturbation of the 60S ribosomal biogenesis by knocking down either L29 or L30 drastically induced the level and activity of p53, leading to p53-depedent cell cycle arrest. Furthermore, this p53 activation requires ribosomal proteins L5 and L11, as knocking down either L5 or L11 completely abolished p53 activation induced by knockdown of L29 or L30. Consistently, knockdown of L29 or L30 enhances the interaction of MDM2 with L5 and L11. These results suggest that direct perturbation of the 60S ribosomal biogenesis activates p53 via L5 and L11-mediated MDM2 suppression.

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 1104.