Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer

Nat Rev Mol Cell Biol. 2008 Oct;9(10):759-69. doi: 10.1038/nrm2514.

Abstract

First described over 80 years ago, ataxia-telangiectasia (A-T) was defined as a clinical entity 50 years ago. Although not encountered by most clinicians, it is a paradigm for cancer predisposition and neurodegenerative disorders and has a central role in our understanding of the DNA-damage response, signal transduction and cell-cycle control. The discovery of the protein A-T mutated (ATM) that is deficient in A-T paved the way for rapid progress on understanding how ATM functions with a host of other proteins to protect against genome instability and reduce the risk of cancer and other pathologies.

Publication types

  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia / complications
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / physiopathology*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Genetic Predisposition to Disease
  • Humans
  • Insulin Resistance
  • Metabolic Syndrome / etiology
  • Mice
  • Models, Biological
  • Mutation
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Nerve Degeneration
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • Signal Transduction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein Serine-Threonine Kinases