DOI: 10.1101/gad.913001. 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

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

10.1101/gad.913001

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

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 β-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.

Bibliography

Yamashita, A., Ohnishi, T., Kashima, I., Taya, Y., & Ohno, S. (2001). 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. Genes & Development, 15(17), 2215â2228.

Authors 5

Akio Yamashita (first)
Tetsuo Ohnishi (additional)
Isao Kashima (additional)
Yoichi Taya (additional)
Shigeo Ohno (additional)

References 46 Referenced 346

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{'key': '2021111507421577000_15.17.2215.3', 'first-page': '743', 'article-title': 'Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation.', 'volume': '7', 'author': 'Bodner', 'year': '1992', 'journal-title': 'Oncogene'} / Oncogene / Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. by Bodner (1992)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited	3 years, 9 months ago (Nov. 15, 2021, 10:44 a.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 7:08 a.m.)
Issued	24 years ago (Sept. 1, 2001)
Published	24 years ago (Sept. 1, 2001)
Published Online	24 years ago (Sept. 1, 2001)
Published Print	24 years ago (Sept. 1, 2001)

Funders 0

None

BibTeX

@article{Yamashita_2001, title={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}, volume={15}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.913001}, DOI={10.1101/gad.913001}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Yamashita, Akio and Ohnishi, Tetsuo and Kashima, Isao and Taya, Yoichi and Ohno, Shigeo}, year={2001}, month=sep, pages={2215–2228} }

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        2001,
        9,
        1
      ]
    ]
  }
}