ATMINistrating ATM signalling: regulation of ATM by ATMIN

Cell Cycle. 2008 Nov 15;7(22):3483-6. doi: 10.4161/cc.7.22.7044. Epub 2008 Nov 18.

Abstract

The checkpoint kinase ATM (ataxia telangiectasia mutated) transduces genomic stress signals to halt cell cycle progression and promote DNA repair in response to DNA damage. We have recently identified an essential cofactor for ATM, ATMIN (for ATM INteractor). Several observations suggested that ATMIN plays a key role in ATM signalling. ATMIN and ATM protein stability were mutually dependent, which indicated an intimate physical and functional interaction. ATMIN bound ATM using a short carboxy-terminal motif, in a manner analogous to how another ATM cofactor, Nijmegen Breakage Syndrome protein 1 (NBS1), associates with ATM. ATMIN and NBS1 had complementary functions in ATM signalling. ATMIN was required for ATM signalling by chloroquine and hypotonic stress, but not after induction of double-stand breaks by ionizing radiation (IR), whereas NBS1 is required for ATM signalling by IR. This suggested competition of NBS1 and ATMIN for ATM binding in a signal-dependent fashion. Some implications of these findings for the ATM signalling pathway are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Carrier Proteins / physiology*
  • Cell Cycle Proteins / immunology
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle Proteins / physiology
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Humans
  • Nuclear Proteins
  • Protein Serine-Threonine Kinases / immunology
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Serine-Threonine Kinases / physiology
  • Signal Transduction*
  • Transcription Factors
  • Tumor Suppressor Proteins / immunology
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / physiology

Substances

  • ATMIN protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases