抄録
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 |
| 巻 | 64 |
| 発行部数 | 9 |
| DOI | |
| 出版物ステータス | Published - 01-05-2004 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells. / Uno, Futoshi; Sasaki, Jiichiro; Nishizaki, Masahiko; Carboni, Giovanni; Xu, Kai; Atkinson, Edward N.; Kondo, Masashi; Minna, John D.; Roth, Jack A.; Ji, Lin.
：: Cancer Research, 巻 64, 番号 9, 01.05.2004, p. 2969-2976.研究成果: Article
TY - JOUR
T1 - Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells
AU - Uno, Futoshi
AU - Sasaki, Jiichiro
AU - Nishizaki, Masahiko
AU - Carboni, Giovanni
AU - Xu, Kai
AU - Atkinson, Edward N.
AU - Kondo, Masashi
AU - Minna, John D.
AU - Roth, Jack A.
AU - Ji, Lin
PY - 2004/5/1
Y1 - 2004/5/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-03-3702
DO - 10.1158/0008-5472.CAN-03-3702
M3 - Article
C2 - 15126327
AN - SCOPUS:2342472611
VL - 64
SP - 2969
EP - 2976
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 9
ER -