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Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis.

Bursac S1, Brdovcak MC1, Donati G2, Volarevic S3.

Biochim Biophys Acta. 2014 ;1842(6):817-30.

1Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.and

2Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Institut d’Investigacio’ Biome’dica de Bellvitge (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain.and

3Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia. Electronic address: [email protected]

 

Abstract

Errors in ribosome biogenesis can result in quantitative or qualitative defects in protein synthesis and consequently lead to improper execution of the genetic program and the development of specific diseases. Evidence has accumulated over the last decade suggesting that perturbation of ribosomebiogenesis triggers a p53-activating checkpoint signaling pathway, often referred to as the ribosome biogenesis stress checkpoint pathway. Although it was originally suggested that p53 has a prominent role in preventing diseases by monitoring the fidelity of ribosome biogenesis, recent work has demonstrated that p53 activation upon impairment of ribosome biogenesis also mediates pathological manifestations in humans. Perturbations ofribosome biogenesis can trigger a p53-dependent checkpoint signaling pathway independent of DNA damage and the tumor suppressor ARF through inhibitory interactions of specific ribosomal components with the p53 negative regulator, Mdm2. Here we review the recent advances made toward understanding of this newly-recognized checkpoint signaling pathway, its role in health and disease, and discuss possible future directions in this exciting research field. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.

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