NM-1, a c-Myc-binding Protein, Is a Candidate for a Tumor Suppressor in Leukemia/Lymphoma and Tongue Cancer

Yuko Fujioka, Takahiro Taira, Yuichi Maeda, Shinya Tanaka, Hiroshi Nishihara, Sanae M.M. Iguchi-Ariga, Kazuo Nagashima, Hiroyoshi Ariga

Research output: Contribution to journalArticle

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Abstract

The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence, and it plays key functions in cell proliferation, differentiation, and apoptosis. We previously showed that MM-1 bound to myc box II within the transactivation domain of c-Myc and repressed the E-box-dependent transcriptional activity of c-Myc. Here we report that MM-1 showed features of a tumor suppressor. In an EST data base search for cDNAs homologous to MM-1, we found a frequent substitution of amino acid 157 of MM-1, from alanine to arginine (A157R), and the substitution was observed more in tumor cells than in normal cells. A survey of the A157R mutation of MM-1 in 57 cultured cancer cells and 90 tissues from cancer patients showed that the A157R was present in about 50-60% of leukemia/lymphoma cells and in more than 75% of squamous cell carcinoma of tongue cancer. Although both the A157R and the wild-type MM-1 bound to c-Myc, only A157R lost the activities to repress both the E-box-dependent transcriptional activity of c-Myc and the myc/ras cooperative transforming activity in rat 3Y1 cells. Furthermore, the wild-type MM-1, but not A157R, arrested the growth of 3Y1 cells. The human MM-1 gene was mapped at chromosome 12q12-12q13, where many chromosome abnormalities in cancer cells have been reported. The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc.

Original languageEnglish
Pages (from-to)45137-45144
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number48
DOIs
Publication statusPublished - 2001 Nov 30
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-myc
Tongue Neoplasms
Tumors
Lymphoma
Carrier Proteins
Leukemia
Cells
Chromosomes
Substitution reactions
E-Box Elements
Neoplasms
Oncogene Proteins
Expressed Sequence Tags
Cell proliferation
Alanine
Arginine
Rats
Transcription Factors
Complementary DNA
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

NM-1, a c-Myc-binding Protein, Is a Candidate for a Tumor Suppressor in Leukemia/Lymphoma and Tongue Cancer. / Fujioka, Yuko; Taira, Takahiro; Maeda, Yuichi; Tanaka, Shinya; Nishihara, Hiroshi; Iguchi-Ariga, Sanae M.M.; Nagashima, Kazuo; Ariga, Hiroyoshi.

In: Journal of Biological Chemistry, Vol. 276, No. 48, 30.11.2001, p. 45137-45144.

Research output: Contribution to journalArticle

Fujioka, Y, Taira, T, Maeda, Y, Tanaka, S, Nishihara, H, Iguchi-Ariga, SMM, Nagashima, K & Ariga, H 2001, 'NM-1, a c-Myc-binding Protein, Is a Candidate for a Tumor Suppressor in Leukemia/Lymphoma and Tongue Cancer', Journal of Biological Chemistry, vol. 276, no. 48, pp. 45137-45144. https://doi.org/10.1074/jbc.M106127200
Fujioka, Yuko ; Taira, Takahiro ; Maeda, Yuichi ; Tanaka, Shinya ; Nishihara, Hiroshi ; Iguchi-Ariga, Sanae M.M. ; Nagashima, Kazuo ; Ariga, Hiroyoshi. / NM-1, a c-Myc-binding Protein, Is a Candidate for a Tumor Suppressor in Leukemia/Lymphoma and Tongue Cancer. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 48. pp. 45137-45144.
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