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

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2969-2976
Number of pages8
JournalCancer Research
Issue number9
Publication statusPublished - 01-05-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells'. Together they form a unique fingerprint.

Cite this