title: The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control.
abstract: Bloom syndrome is an autosomal recessive disorder associated with mutations in BLM gene encoding protein that belongs to the family of DNA helicases. It is characterized by predisposition to cancer, immunodeficiency, high sensitivity to UV and genomic instability of somatic cells. Here we show physical and functional cooperation between BLM and p53 proteins. Ectopic expression of BLM causes anti-proliferative effect in p53 wild type, but not in p53-deficient cells; p53-mediated transactivation is attenuated in primary fibroblasts from Bloom syndrome patients. BLM and p53 proteins physically interact in the cells as demonstrated in yeast and mammalian two-hybrid systems; interaction sites are mapped to 237-272 aa residues of BML and 285-340 aa of p53. Ectopic expression of the fragment of wild type BML containing p53-interactive domain suppresses p53-mediated transcription and interferes with p53-mediated growth inhibition. These observations indicate that BLM might be an important component of p53 function and suggest that Bloom Syndrome phenotype may in part be the result of the deregulation of the p53 tumor suppressor pathway.
authors.affiliation: Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: I V
authors.initials: IV
authors.lastname: Garkavtsev
authors.forename: N
authors.initials: N
authors.lastname: Kley
authors.forename: I A
authors.initials: IA
authors.lastname: Grigorian
authors.forename: A V
authors.initials: AV
authors.lastname: Gudkov
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D001665:Binding Sites; D001816:Bloom Syndrome / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D016159:Tumor Suppressor Protein p53; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases