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Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a conserved surveillance mechanism that eliminates imperfect mRNAs that contain premature translation termination codons (PTCs) and code for nonfunctional or potentially harmful polypeptides. We show that a novel phosphatidylinositol 3-kinase-related protein kinase, hSMG-1, is a human ortholog of a product of Caenorhabditis elegans smg-1, one of seven smg genes involved in NMD. hSMG-1 phosphorylates hUPF1/SMG-2 in vivo and in vitro at specific serine residues in SQ motifs. hSMG-1 can associate with hUPF1/SMG-2 and other components of the surveillance complex. In particular, overexpression of a kinase-deficient point mutant of hSMG-1, hSMG-1-DA, results in a marked suppression of the PTC-dependent beta-globin mRNA degradation; whereas that of wild-type hSMG-1 enhances it. We also show that inhibitors of hSMG-1 induce the accumulation of truncated p53 proteins in human cancer cell lines with p53 PTC mutation. Taken together, we conclude that hSMG-1 plays a critical role in NMD through the direct phosphorylation of hUPF1/SMG-2 in the evolutionally conserved mRNA surveillance complex.

Pubmed ID: 11544179


  • Yamashita A
  • Ohnishi T
  • Kashima I
  • Taya Y
  • Ohno S


Genes & development

Publication Data

September 1, 2001

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Caenorhabditis elegans
  • Cell Line
  • Cloning, Molecular
  • DNA, Complementary
  • Dose-Response Relationship, Drug
  • Globins
  • HeLa Cells
  • Humans
  • Metalloendopeptidases
  • Models, Genetic
  • Molecular Sequence Data
  • Multigene Family
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phylogeny
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Biosynthesis
  • Protein Isoforms
  • Protein Kinases
  • RNA, Messenger
  • Sequence Homology, Amino Acid
  • Time Factors
  • Transfection