The ATM-related kinase, hSMG-1, bridges genome and RNA surveillance pathways.
Recent studies have identified, hSMG-1 as the newest member of the phosphoinositide 3-kinase(PI3-kinase)-related kinase (PIKK) family. The protein kinase activity of hSMG-1 resembles that of the related PIKK, ATM, both in terms of substrate specificity and its sensitivity to inhibition by the fungal metabolite wortmannin. hSMG-1 is the ortholog of a Caenorhabditis elegans protein, CeSMG-1, which has been genetically linked to a critical mRNA surveillance pathway termed nonsense-mediated decay (NMD). The function of NMD is to mark for rapid degradation mRNAs that bear a premature termination codon. Compelling evidence now indicates that hSMG-1 is also a central player in the NMD pathway in human cells. In addition, hSMG-1, like ATM, appears to be involved in the recognition and/or repair of damaged DNA in these cells. In this review, we introduce a model in which hSMG-1 teams with ATM and ATR to insure the overall quality of the transcriptome in human cells.
Program in Signal Transduction Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92130, USA. abraham@burnham.org
Robert T
RT
Abraham
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D017173:Caenorhabditis elegans; D018797:Cell Cycle Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D016678:Genome; D006801:Humans; D008666:Metalloendopeptidases; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D012313:RNA; D011494:Protein Kinases; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase