title: Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis.
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 ribosome biogenesis 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 of ribosome 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.
authors: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors: Sladana
authors: S
authors: Bursac
authors: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors: Maja Cokaric
authors: MC
authors: Brdovcak
authors: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Institut d'Investigacio' Biome'dica de Bellvitge (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain.
authors: Giulio
authors: G
authors: Donati
authors: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia. Electronic address: sinisa.volarevic@medri.uniri.hr.
authors: Sinisa
authors: S
authors: Volarevic
mesh_terms: D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D006801:Humans; D014176:Protein Biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: 5S rRNA; RPL11; RPL5; Ribosome biogenesis stress; Ribosomopathies; p53