TY - JOUR
T1 - p53 acts as a safeguard of translational control by regulating fibrillarin and rRNA methylation in cancer
AU - Marcel, Virginie
AU - Ghayad, Sandra E.
AU - Belin, Stéphane
AU - Therizols, Gabriel
AU - Morel, Anne-Pierre
AU - Solano-Gonzàlez, Eduardo
AU - Vendrell, Julie A.
AU - Hacot, Sabine
AU - Mertani, Hichem C.
AU - Albaret, Marie Alexandra
AU - Bourdon, Jean-Christophe
AU - Jordan, Lee
AU - Thompson, Alastair
AU - Tafer, Yasmine
AU - Cong, Rong
AU - Bouvet, Philippe
AU - Saurin, Jean-Christophe
AU - Catez, Frédéric
AU - Prats, Anne-Catherine
AU - Puisieux, Alain
AU - Diaz, Jean-Jacques
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/9/9
Y1 - 2013/9/9
N2 - Ribosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.
AB - Ribosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.
U2 - 10.1016/j.ccr.2013.08.013
DO - 10.1016/j.ccr.2013.08.013
M3 - Article
C2 - 24029231
SN - 1535-6108
VL - 24
SP - 318
EP - 330
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -