ATMINistrating ATM signalling: regulation of ATM by ATMIN.
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.
Kanu
Nnennaya
N
Mammalian Genetics Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom.
Behrens
Axel
A
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology
C522841:ATMIN protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases