title: Nucleolar stress in Diamond Blackfan anemia pathophysiology.
abstract: Diamond Blackfan anemia is a red cell hypoplasia that typically presents within the first year of life. Most cases of Diamond Blackfan anemia are caused by ribosome assembly defects linked to haploinsufficiency for structural proteins of either ribosomal subunit. Nucleolar stress associated with abortive ribosome assembly leads to p53 activation via the interaction of free ribosomal proteins with HDM2, a negative regulator of p53. Significant challenges remain in linking this nucleolar stress signaling pathway to the clinical features of Diamond Blackfan anemia. Defining aspects of disease presentation may relate to developmental and physiological triggers that work in conjunction with nucleolar stress signaling to heighten the p53 response in the developing erythron after birth. The growing number of ribosomopathies provides additional challenges for linking molecular mechanisms with clinical phenotypes. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292, USA. Electronic address: srellis@louisville.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ellis
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009154:Mutation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
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: Anemia; Haploinsufficiency; Nucleolar stress; Ribosomopathy