Published on Sept. 9, 2013 in Cancer Cell volume 24(3).

PubMed ID: 24029231

DOI: S1535-6108(13)00359-0

Abstract:

Ribosomes are specialized entities that participate in regulation of gene expressionthrough their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivatedin p53-inactivated cancer cells, although involvement of p53 on ribosome quality isunknown. Here, we show that p53 represses expression of the rRNA methyl-transferasefibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied bymodifications of the rRNA methylation pattern, impairment of translational fidelity,and an increase of internal ribosome entry site (IRES)-dependent translationinitiation of key cancer genes. FBL overexpression contributes to tumorigenesis andis associated with poor survival in patients with breast cancer. Thus, p53 acts as asafeguard of protein synthesis by regulating FBL and the subsequent quality andintrinsic activity of ribosomes.CI - Copyright © 2013 Elsevier Inc. All rights reserved.