ATM associates with and phosphorylates p53: mapping the region of interaction

@article{Khanna1998ATMAW,
  title={ATM associates with and phosphorylates p53: mapping the region of interaction},
  author={Kum Kum Khanna and Katherine E. Keating and Sergei V. Kozlov and Shaun P. Scott and Magtouf Gatei and Karen Hobson and Yoichi Taya and Brian G Gabrielli and Doug W. Chan and Susan P. Lees-Miller and Martin F. Lavin},
  journal={Nature Genetics},
  year={1998},
  volume={20},
  pages={398-400}
}
The human genetic disorder ataxia-telangiectasia (AT) is characterized by immunodeficiency, progressive cerebellar ataxia, radiosensitivity, cell cycle checkpoint defects and cancer predisposition. The gene mutated in this syndrome, ATM (for AT mutated), encodes a protein containing a phosphatidyl-inositol 3-kinase (PI-3 kinase)-like domain. ATM also contains a proline-rich region and a leucine zipper, both of which implicate this protein in signal transduction. The proline-rich region has been… Expand
ATM: the product of the gene mutated in ataxia-telangiectasia.
  • M. Lavin
  • Biology, Medicine
  • The international journal of biochemistry & cell biology
  • 1999
TLDR
It is clear that a better definition of the role of ATM in DNA damage recognition, cell cycle control and cell signalling may assist in the treatment of the progressive neurodegeneration in this syndrome. Expand
ATM: the protein encoded by the gene mutated in the radiosensitive syndrome ataxia-telangiectasia.
TLDR
It is evident that a small number of residual strand breaks remain unrepaired in A-T cells, which may well account for the radiosensitivity, and emerging evidence supports a direct role for ATM at other cell cycle checkpoints. Expand
Purification and DNA binding properties of the ataxia-telangiectasia gene product ATM.
  • G. Smith, R. B. Cary, +4 authors S. Jackson
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
The results provide a biochemical assay system for ATM, support genetic data indicating distinct roles for DNA-dependent protein kinase and ATM, and suggest how ATM may signal the presence of DNA damage to p53 and other downstream effectors. Expand
Is Ataxia Telangiectasia a Result of Impaired Coordination between DNA Repair and Cell Cycle Checkpoint Regulators
TLDR
The scope of this review is focused on the potential functions of ATM in both DNA repair and cell cycle checkpoint regulation and how deficiencies in these overlapping functions can lead to some of the phenotypic features of AT patients. Expand
Purification and Characterization of ATM from Human Placenta
TLDR
Highly purified ATM phosphorylated PHAS-I, the 32-kDa subunit of RPA, serine 15 of p53, and Chk2 in vitro, suggesting that the requirement for manganese is a characteristic of this class of enzyme. Expand
Functional consequences of sequence alterations in the ATM gene.
TLDR
The domain structure of the ATM molecule, sites of interaction with other proteins and the consequences of specific amino acid changes on function are explored. Expand
Influence of ATM Function on Interactions between Telomeres and Nuclear Matrix1
TLDR
The results suggest that the ATM gene influences the interactions between telomeres and the nuclear matrix and that alterations in telomere chromatin could be at least partly responsible for the pleiotropic phenotypes of the ATM genes. Expand
ATM Phosphorylates and Activates the Transcription Factor MEF2D for Neuronal Survival in Response to DNA Damage
TLDR
Results suggest that ATM associates with MEF2D and activates its activity via phosphorylation, thus promoting neuronal survival in response to DNA damage. Expand
Identification of Domains of Ataxia-telangiectasia Mutated Required for Nuclear Localization and Chromatin Association*
TLDR
It is shown that the recruitment/retention of ATM at DSBs requires its kinase activity because a kinase-dead mutant of GFP·ATM failed to form damage-induced foci, demonstrating that the ATM amino terminus is required for optimal ATM function. Expand
The Role of ATM in Telomere Structure and Function
TLDR
This paper summarizes the recent publications and presents some new data on the influence of ATM on telomere metabolism, which found a link was also found between alteredTelomere–nuclear matrix interactions, aberrant Telomere clustering, and gonadal atrophy. Expand
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References

SHOWING 1-10 OF 23 REFERENCES
Interaction between ATM protein and c-Abl in response to DNA damage
TLDR
It is shown that ATM binds c-Abl constitutively in control cells but not in AT cells, and this interaction may in part mediate radiation-induced Gl arrest. Expand
Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms
TLDR
Evidence that ATM protein binds to p53 and this association is defective in A-T cells compatible with the defective p53 response in these cells is provided, providing further support for a role for the ATM protein as a sensor of DNA damage and in a more general role in cell signalling,compatible with the broader phenotype of the syndrome. Expand
Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation
TLDR
These findings identify the c-Abl tyrosine kinase as a downstream target of phosphorylation and activation by the ATM kinase in the cellular response to ionizing radiation. Expand
A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
TLDR
A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia was identified by positional cloning on chromosome 11q22-23 and encoded a putative protein that is similar to several yeast and mammalian phosphatidylinositol-3' kinases that are involved in mitogenic signal transduction, meiotic recombination, and cell cycle control. Expand
Isolation of full-length ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype.
  • N. Zhang, P. Chen, +7 authors M. Lavin
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
Overexpression of ATM cDNA in A-T cells enhanced the survival of these cells in response to radiation exposure, decreased radiation-induced chromosome aberrations, reduced radio-resistant DNA synthesis, and partially corrected defective cell cycle checkpoints and induction of stress-activated protein kinase. Expand
Fragments of ATM which have dominant-negative or complementing activity
TLDR
expression of the carboxy-terminal portion of ATM, which contains the PI-3 kinase domain, complemented radiosensitivity and the S-phase checkpoint and reduced chromosomal breakage after irradiation in AT cells, suggesting that ATM function is dependent on interactions with itself or other proteins through the leucine zipper region. Expand
The genetic defect in ataxia-telangiectasia.
TLDR
The pleiotropic nature of the clinical and cellular phenotype suggests that the gene product involved is important in maintaining stability of the genome but also plays a more general role in signal transduction. Expand
Cloning and expression of the ataxia-telangiectasia gene in baculovirus.
TLDR
It is demonstrated that ATM can be expressed inefficiently in baculovirus infected insect cells and the data suggest that it phosphorylates itself. Expand
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
TLDR
Three participants are identified (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development. Expand
ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins
TLDR
This data indicates that the p53 tumour-suppressor protein is a sequence-specific DNA-binding transcription factor that induces cell cycle arrest or apoptosis in response to genotoxic stress and that this region of p53 is targeted by DNA-damage signalling pathways in vivo. Expand
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