Keywords: Atm, Dna Damage, Hmga1, Atm Protein, Glutamine, High Mobility Group A Protein, High Mobility Group A1b Protein, Serine, Amino Acid Sequence, Article, Cell Activity, Cell Cycle, Cell Strain Mcf 7, Cell Survival, Cell Transformation, Chromosome Rearrangement, Clonogenesis, Confocal Laser Microscopy, Confocal Microscopy, Controlled Study, Downstream Processing, Embryo, Enzyme Activation, Enzyme Phosphorylation, Genomic Instability, Human, Human Cell, Ionizing Radiation, Priority Journal, Protein Expression, Protein Localization, Protein Motif, Protein Phosphorylation, Protein Protein Interaction, Protein Targeting, Cell Cycle Proteins, Cell Line, Tumor, Dna-Binding Proteins, Hmga1a Protein, Neoplasms, Protein-Serine-Threonine Kinases, Tumor Suppressor Proteins,
Affiliations: *** IBB - CNR ***
Istituto di Endocrinologia ed Oncologia Sperimentale, CNR Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Via S. Pansini 5, 80131 Naples, Italy
Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, United States
Istituto di Biostrutture e Bioimmagini, CNR, Dipartimento di Diagnostica per Immagini e Radioterapia, Via S. Pansini 5, 80131 Naples, Italy
H. San Raffaele-Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milano, Italy
Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine and Genetics, Boston, MA 02115, United States
Dipartimento di Medicina Sperimentale, II Università di Napoli, 80138 Naples, Italy
Division of Human Cancer Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, OH 43210, United States
Genome Stability, Laboratories, London Research Institute, Clare Hall, South Mimms, Herts EN6 3LD, United Kingdom
NOGEC (Naples Oncogenomic Center), CEINGE, Biotecnologie Avanzate, via Comunale Margherita, 80131 Naples, Italy
References: Not available.
HMGA1 protein is a novel target of the ATM kinase
The high mobility group HMGA1 protein belongs to a family of architectural factors that play a role in chromosomal Organisation and gene transcription regulation. HMGA 1 overexpression represents a common feature of human malignant tumours and is causally associated with neoplastic transformation and metastatic progression. Recently, HMGA1 expression has been correlated with the presence of chromosomal rearrangements and suggested to promote genomic instability. Here, we report a novel interaction between HMGA1 protein and the ataxia-telangiectasia mutated (ATM) kinase, the major key player in the cellular response to DNA damage caused by several agents such as ionising radiation (IR). We identified an SQ motif on HMGA1, which is effectively phosphorylated by ATM in vitro and in vivo. Interestingly, confocal microscopy revealed that HMGA1 colocalises with the activated form of ATM (ATM S1981p). Moreover, HMGA1 ectopic expression decreases cell survival following exposure to IR as assessed by clonogenic survival in MCF-7 cells, further supporting the hypothesis that HMGA1 might act as a downstream target of the ATM pathway in response to DNA damage. (C) 2008 Elsevier Ltd. All rights reserved.
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(454 views) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 ViewExport to BibTeXExport to EndNote