Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells

Futoshi Uno, Jiichiro Sasaki, Masahiko Nishizaki, Giovanni Carboni, Kai Xu, Edward N. Atkinson, Masashi Kondo, John D. Minna, Jack A. Roth, Lin Ji

研究成果: Article

71 引用 (Scopus)

抜粋

FUS1 is a novel tumor suppressor gene identified in the human chromosome 3p21.3 region that is deleted in many cancers. Using surface-enhanced laser desorption/ionization mass spectrometric analysis on an anti-Fus1-antibody-capture ProteinChip array, we identified wild-type Fus1 as an N-myristoylated protein. N-myristoylation is a protein modification process in which a 14-carbon myristoyl group is cotranslationally and covalently added to the NH2-terminal glycine residue of the nascent polypeptide. Loss of expression or a defect of myristoylation of the Fus1 protein was observed in human primary lung cancer and cancer cell lines. A myristoylation-deficient mutant of the Fus1 protein abrogated its ability to inhibit tumor cell-induced clonogenicity in vitro, to induce apoptosis in lung tumor cells, and to suppress the growth of tumor xenografts and lung metastases in vivo and rendered it susceptible to rapid proteasome-dependent degradation. Our results show that myristoylation is required for Fus1-mediated tumor-suppressing activity and suggest a novel mechanism for the inactivation of tumor suppressors in lung cancer and a role for deficient posttranslational modification in tumor suppressor-gene-mediated carcinogenesis.

元の言語English
ページ(範囲)2969-2976
ページ数8
ジャーナルCancer Research
64
発行部数9
DOI
出版物ステータスPublished - 01-05-2004
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Uno, F., Sasaki, J., Nishizaki, M., Carboni, G., Xu, K., Atkinson, E. N., Kondo, M., Minna, J. D., Roth, J. A., & Ji, L. (2004). Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells. Cancer Research, 64(9), 2969-2976. https://doi.org/10.1158/0008-5472.CAN-03-3702