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 journalArticle

71 Citations (Scopus)

Abstract

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
Volume64
Issue number9
DOIs
Publication statusPublished - May 1 2004
Externally publishedYes

Fingerprint

Lung Neoplasms
Neoplasms
Proteins
Tumor Suppressor Genes
Lung
Protein Array Analysis
Human Chromosomes
Proteasome Endopeptidase Complex
Mutant Proteins
Post Translational Protein Processing
Heterografts
Glycine
Anti-Idiotypic Antibodies
Carcinogenesis
Lasers
Carbon
Apoptosis
Neoplasm Metastasis
Cell Line
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

In: Cancer Research, Vol. 64, No. 9, 01.05.2004, p. 2969-2976.

Research output: Contribution to journalArticle

Uno, F, Sasaki, J, Nishizaki, M, Carboni, G, Xu, K, Atkinson, EN, Kondo, M, Minna, JD, Roth, JA & Ji, L 2004, 'Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells', Cancer Research, vol. 64, no. 9, pp. 2969-2976. https://doi.org/10.1158/0008-5472.CAN-03-3702
Uno, Futoshi ; Sasaki, Jiichiro ; Nishizaki, Masahiko ; Carboni, Giovanni ; Xu, Kai ; Atkinson, Edward N. ; Kondo, Masashi ; Minna, John D. ; Roth, Jack A. ; Ji, Lin. / Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells. In: Cancer Research. 2004 ; Vol. 64, No. 9. pp. 2969-2976.
@article{9d48f4bca3fd490fb1d5556faf0b5977,
title = "Myristoylation of the Fus1 Protein Is Required for Tumor Suppression in Human Lung Cancer Cells",
abstract = "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.",
author = "Futoshi Uno and Jiichiro Sasaki and Masahiko Nishizaki and Giovanni Carboni and Kai Xu and Atkinson, {Edward N.} and Masashi Kondo and Minna, {John D.} and Roth, {Jack A.} and Lin Ji",
year = "2004",
month = "5",
day = "1",
doi = "10.1158/0008-5472.CAN-03-3702",
language = "English",
volume = "64",
pages = "2969--2976",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=2342472611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342472611&partnerID=8YFLogxK

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 - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 9

ER -