Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L) encoding a protein homologous to human NIP3
Mieko Matsushima
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Department of Gynecology and Obstetrics, Nagoya City University, Nagoya, Japan
Search for more papers by this authorTsutomu Fujiwara
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
Search for more papers by this authorEi-ichi Takahashi
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
Search for more papers by this authorTakeo Minaguchi
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorYutaka Eguchi
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorYoshihide Tsujimoto
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorKaoru Suzumori
Department of Gynecology and Obstetrics, Nagoya City University, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Yusuke Nakamura
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, JapanSearch for more papers by this authorMieko Matsushima
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Department of Gynecology and Obstetrics, Nagoya City University, Nagoya, Japan
Search for more papers by this authorTsutomu Fujiwara
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
Search for more papers by this authorEi-ichi Takahashi
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan
Search for more papers by this authorTakeo Minaguchi
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorYutaka Eguchi
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorYoshihide Tsujimoto
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorKaoru Suzumori
Department of Gynecology and Obstetrics, Nagoya City University, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Yusuke Nakamura
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, JapanSearch for more papers by this authorAbstract
We have isolated a novel cDNA that encodes a product showing significant sequence homology (56% identity) to human NIP3, a protein thought to interact with adenovirus E1B19kD and human BCL2 proteins. This cDNA contains an open reading frame of 657 nucleotides encoding a 219 amino acid polypeptide. The gene, designated BNIP3L, was expressed in all 16 normal human tissues examined; we mapped it to chromosome band 8p21 by fluorescence in situ hybridization. Introduction of the BNIP3L gene into six different cancer-cell lines caused significant growth suppression in each of them, while no such effect occurred when the antisense cDNA or the vector DNA was transfected, indicating that BNIP3L may function as a tumor suppressor. Genes Chromosomes Cancer 21:230–235, 1998. © 1998 Wiley-Liss, Inc.
References
- Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y (1994) Multiple subcellular localization of bcl-2: Detection in nuclear outer membrane endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res 54: 2468–2471.
- Benham FJ, Harris H (1979) Human cell lines expressing intestinal alkaline phosphatase. Proc Natl Acad Sci USA 76: 4016–4019.
- Bova GS, Carter BS, Bussemakers MJG, Emi M, Fujiwara Y, Kyprianou N, Jacobs S, Robinson JC, Epstein JI, Walsh PC, Isaaacs WB (1993) Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res 53: 3869–3873.
- Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D'Sa-Eipper C, Chinnadurai G (1994) Adenovirus E1B 19kDa and Bcl-2 proteins interact with a common set of cellular proteins. Cell 79: 341–351.
- Debbas M, White E (1993) Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev 7: 546–554.
- Emi M, Fujiwara Y, Nakajima T, Tsuchiya E, Tsuda H, Hirohashi S, Maeda Y, Tsuruta K, Miyaki M, Nakamura Y (1992) Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer. Cancer Res 52: 5368–5372.
- Emi M, Fujiwara Y, Ohata H, Tsuda H, Hirohashi S, Koike M, Miyaki M, Monden M, Nakamura Y (1993) Allelic loss at chromosome band 8p21.3-p22 is associated with progression of hepatocellular carcinoma. Genes Chromosomes Cancer 7: 152–157.
- Fernandez-Sarabia MJ, Bischoff JR (1993) Bcl-2 associates with the ras related protein R-ras p23. Nature 366: 274–275.
- Fujiwara Y, Emi M, Ohata H, Kato Y, Nakajima T, Mori T, Nakamura Y (1993) Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma. Cancer Res 53: 1172–1174.
- Fujiwara Y, Ohata H, Emi M, Okui K, Koyama K, Tsuchiya E, Nakajima T, Monden M, Mori T, Kurimasa A, Nakamura Y (1994) A 3-Mb physical map of the chromosome region 8p21.3-p22, including a 600-kb region commonly deleted in human hepatocellular carcinoma, colorectal cancer, and non-small cell lung cancer. Genes Chromosomes Cancer 10: 7–14.
- Huang DCS, Cory S, Strasser A (1997) Bcl-2, Bcl-XL, and adenovirus protein E1B 19kD are functionally equivalent in their ability to inhibit cell death. Oncogene 14: 405–414.
- Inazawa J, Saito H, Ariyama T, Abe T, Nakamura Y (1993) High-resolution cytogenetic mapping of 342 new cosmid markers including 43 RFLP markers on human chromosome 17 by fluorescence in situ hybridization. Genomics 17: 153–162.
- Kroemer G (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3: 614–620.
- Leibovitz A, Stinson JC, McCombs WB, McCoy CE, Mazur KC, Mabry ND (1976) Classification of human colorectal adenocarci-noma cell lines. Cancer Res 36: 4562–4569.
- Macoska JA, Trybus TM, Sakr WA, Wolf MC, Benson PD, Powell IJ, Pontes JE (1994) Fluorescence in situ hybridization analysis of 8p allelic loss and chromosome 8 instability in human prostate cancer. Cancer Res 54: 3824–3830.
- Nakai K, Kanehisa M (1991) Expert system for predicting protein localization sites in gram negative bacteria. Proteins 11: 95–110.
- Nakai K, Kanehisa M (1992) A knowledge base for predicting protein localization sites in eukaryotic cells. Genomics 14: 897–911.
- Ohata H, Emi M, Fujiwara Y, Higashino K, Nakagawa K, Futagami R, Tsuchiya E, Nakamura Y (1993) Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma. Genes Chromosomes Cancer 7: 85–88.
- Pearson WR, Lipman DJ (1988) Improved tools for biological sequence analysis. Proc Natl Acad Sci USA 85: 1435–1441.
- Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E (1992) The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci USA 89: 7742–7746.
- Stein GH (1979) T98G: An anchorage-independent human tumor cell line that exhibits stationary phase G1 arrest in vitro. J Cell Physiol 99: 43–54.
- Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC (1995) Cloning and functional analysis of BAG-1: A novel Bcl-2 binding protein with anti-cell death activity. Cell 80: 279–284.
- Tarodi B, Subramanian T, Chinnadurai G (1993) Functional similarity between adenovirus E1B 19K gene and Bcl2 oncogene: Mutant complementation and suppression of cell death induced by DNA damaging agents. Int J Oncol 3: 467–472.
- Wang HG, Miyashita T, Takayama S, Sato T, Torigoe T, Krajewski S, Tanaka S, Hovey L, Troppmair J, Rapp UR, Reed JC (1994) Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene 9: 2751–2756.
- Wang HG, Takayama S, Rapp UR, Reed JC (1996) Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci USA 93: 7063–7068.