Molecules and Cells

  • 제21권1호
  • /
  • Pages.1-6
  • /
  • 2006
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

Regulation of BNIP3 in Normal and Cancer Cells

  • Lee, Hayyoung (Institute of Biotechnology, Chungnam National University) ;
  • Paik, Sang-Gi (Department of Biology, School of Biosciences and Biotechnology, Chungnam National University)
  • 발행 : 2006.02.28
⟨ 이전 논문 다음 논문 ⟩

초록

Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.

키워드

과제정보

연구 과제 주관 기관 : Korea Research Foundation

참고문헌

  1. Abe, T., Toyota, M., Suzuki, H., Murai, M., Akino, K., et al. (2005) Upregulation of BNIP3 by 5-aza-2'-deoxycytidine sensitizes pancreatic cancer cells to hypoxia-mediated cell death. J. Gastroenterol. 40, 504-510 https://doi.org/10.1007/s00535-005-1576-1
  2. Agani, F. H., Puchowicz, M., Chavez, J. C., Pichiule, P., and LaManna, J. (2002) Role of nitric oxide in the regulation of HIF-1alpha expression during hypoxia. Am. J. Physiol. Cell Physiol. 283, C178−186 https://doi.org/10.1152/ajpcell.00174.2002
  3. Akada, M., Crnogorac-Jurcevic, T., Lattimore, S., Mahon, P., Lopes, R., et al. (2005) Intrinsic chemoresistance to gemcitabine is associated with decreased expression of BNIP3 in pancreatic cancer. Clin. Cancer Res. 11, 3094−3101
  4. Bacon, A. L. and Harris, A. L. (2004) Hypoxia-inducible factors and hypoxic cell death in tumour physiology. Ann. Med. 36, 530−539 https://doi.org/10.1080/07853890410018231
  5. Baetz, D., Regula, K. M., Ens, K., Shaw, J., Kothari, S., et al. (2005) Nuclear factor-kappaB-mediated cell survival involves transcriptional silencing of the mitochondrial death gene BNIP3 in ventricular myocytes. Circulation 112, 3777−3785 https://doi.org/10.1161/CIRCULATIONAHA.105.573899
  6. Blouin, C. C., Page, E. L., Soucy, G. M., and Richard, D. E. (2004) Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1 alpha. Blood 103, 1124-1130 https://doi.org/10.1182/blood-2003-07-2427
  7. Boyd, J. M., Malstrom, S., Subramanian, T., Venkatesh, L. K., Schaeper, U., et al. (1994) Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins. Cell 79, 341−351 https://doi.org/10.1016/0092-8674(94)90393-X
  8. Bruick, R. K. (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97, 9082−9087
  9. Burton, T. R., Henson, E. S., Baijal, P., Eisenstat, D. D., and Gibson, S. B. (2005) The pro-cell death Bcl-2 family member, BNIP3, is localized to the nucleus of human glial cells: Implications for glioblastoma multiforme tumor cell survival under hypoxia. Int. J. Cancer 118, 1660−1669 https://doi.org/10.1002/ijc.21547
  10. Chen, G., Ray, R., Dubik, D., Shi, L., Cizeau, J., et al. (1997) The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis. J. Exp. Med. 186, 1975−1983 https://doi.org/10.1084/jem.186.1.1
  11. Chen, G., Cizeau, J., Vande Velde, C., Park, J. H., Bozek, G., et al. (1999) Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins. J. Biol. Chem. 274, 7-10 https://doi.org/10.1074/jbc.274.1.7
  12. Chun, Y. S., Kim, M. S., and Park, J. W. (2002) Oxygendependent and -independent regulation of HIF-1alpha. J. Korean. Med. Sci. 17, 581−588
  13. Crow, M. T. (2002) Hypoxia, BNip3 proteins, and the mitochondrial death pathway in cardiomyocytes. Circ. Res. 91, 183−185 https://doi.org/10.1161/01.RES.0000026600.67226.92
  14. de Angelis, P. M., Fjell, B., Kravik, K. L., Haug, T., Tunheim, S. H., et al. (2004) Molecular characterizations of derivatives of HCT116 colorectal cancer cells that are resistant to the chemotherapeutic agent 5-fluorouracil. Int. J. Oncol. 24, 1279−1288
  15. Erkan, M., Kleeff, J., Esposito, I., Giese, T., Ketterer, K., et al. (2005) Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis. Oncogene 24, 4421−4432 https://doi.org/10.1038/sj.onc.1208642
  16. Fei, P., Wang, W., Kim, S. H., Wang, S., Burns, T. F., et al. (2004) Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell 6, 597−609 https://doi.org/10.1016/j.ccr.2004.10.012
  17. Giatromanolaki, A., Koukourakis, M. I., Sowter, H. M., Sivridis, E., Gibson, S., et al. (2004) BNIP3 expression is linked with hypoxia-regulated protein expression and with poor prognosis in non-small cell lung cancer. Clin. Cancer Res. 10, 5566−5571 https://doi.org/10.1158/1078-0432.CCR-1218-3
  18. Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., et al. (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379, 88-91 https://doi.org/10.1038/379088a0
  19. Guo, K., Searfoss, G., Krolikowski, D., Pagnoni, M., Franks, C., et al. (2001) Hypoxia induces the expression of the proapoptotic gene BNIP3. Cell Death. Differ. 8, 367-376 https://doi.org/10.1038/sj.cdd.4400810
  20. Guscetti, F., Nath, N., and Denko, N. (2005) Functional characterization of human proapoptotic molecules in yeast S. cerevisiae. FASEB J. 19, 464−466
  21. Hemish, J., Nakaya, N., Mittal, V., and Enikolopov, G. (2003) Nitric oxide activates diverse signaling pathways to regulate gene expression. J. Biol. Chem. 278, 42321−42329 https://doi.org/10.1074/jbc.M308192200
  22. Kanzawa, T., Zhang, L., Xiao, L., Germano, I. M., Kondo, Y., et al. (2005) Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene 24, 980−991 https://doi.org/10.1038/sj.onc.1208017
  23. Kennedy, A. S., Harrison, G. H., Mansfield, C. M., Zhou, X. J., Xu, J. F., et al. (2000) Survival of colorectal cancer cell lines treated with paclitaxel, radiation, and 5-FU: effect of TP53 or hMLH1 deficiency. Int. J. Cancer 90, 175−185 https://doi.org/10.1002/(SICI)1097-0215(20000220)90:1<1::AID-IJC1>3.0.CO;2-W
  24. Kim, J. Y., Cho, J. J., Ha, J., and Park, J. H. (2002) The carboxy terminal C-tail of BNip3 is crucial in induction of mitochondrial permeability transition in isolated mitochondria. Arch. Biochem. Biophys. 398, 147-152 https://doi.org/10.1006/abbi.2001.2673
  25. Kimura, H., Weisz, A., Kurashima, Y., Hashimoto, K., Ogura, T., et al. (2000) Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor- 1 activity by nitric oxide. Blood 95, 189−197
  26. Kothari, S., Cizeau, J., McMillan-Ward, E., Israels, S. J., Bailes, M., et al. (2003) BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF. Oncogene 22, 4734−4744 https://doi.org/10.1038/sj.onc.1206666
  27. Kubasiak, L. A., Hernandez, O. M., Bishopric, N. H., and Webster, K. A. (2002) Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc. Natl. Acad. Sci. USA 99, 12825−12830
  28. Lamy, L., Ticchioni, M., Rouquette-Jazdanian, A. K., Samson, M., Deckert, M., et al. (2003) CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis. J. Biol. Chem. 278, 23915−23921 https://doi.org/10.1074/jbc.M301869200
  29. Marsden, V. S. and Strasser, A. (2003) Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. Annu. Rev. Immunol. 21, 71−105 https://doi.org/10.1146/annurev.immunol.21.120601.140933
  30. Mateo, J., Garcia-Lecea, M., Cadenas, S., Hernandez, C., and Moncada, S. (2003) Regulation of hypoxia-inducible factor- 1alpha by nitric oxide through mitochondria-dependent and - independent pathways. Biochem. J. 376, 537−544 https://doi.org/10.1042/BJ20031327
  31. Matsushima, M., Fujiwara, T., Takahashi, E., Minaguchi, T., Eguchi, Y., et al. (1998) Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L) encoding a protein homologous to human NIP3. Genes Chromosomes Cancer 21, 230-235 https://doi.org/10.1002/(SICI)1098-2264(199803)21:3<230::AID-GCC7>3.0.CO;2-0
  32. Metzen, E., Zhou, J., Jelkmann, W., Fandrey, J., and Brune, B. (2003) Nitric oxide impairs normoxic degradation of HIF- 1alpha by inhibition of prolyl hydroxylases. Mol. Biol. Cell. 14, 3470−3481 https://doi.org/10.1091/mbc.E02-06-0327
  33. Mizutani, A., Furukawa, T., Adachi, Y., Ikehara, S., and Taketani, S. (2002) A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis. J. Biol. Chem. 277, 15851-15858 https://doi.org/10.1074/jbc.M111431200
  34. Murai, M., Toyota, M., Satoh, A., Suzuki, H., Akino, K., et al. (2005a) Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours. Br. J. Cancer 92, 1165−1172 https://doi.org/10.1038/sj.bjc.6602422
  35. Murai, M., Toyota, M., Suzuki, H., Satoh, A., Sasaki, Y., et al. (2005b) Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. Clin. Cancer Res. 11, 1021−1027
  36. Okami, J., Simeone, D. M., and Logsdon, C. D. (2004) Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res. 64, 5338−5346 https://doi.org/10.1158/0008-5472.CAN-04-0089
  37. Palmer, L. A., Gaston, B., and Johns, R. A. (2000) Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides. Mol. Pharmacol. 58, 1197−1203
  38. Piret, J. P., Mottet, D., Raes, M., and Michiels, C. (2002) Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem. Pharmacol. 64, 889-892 https://doi.org/10.1016/S0006-2952(02)01155-3
  39. Ray, R., Chen, G., Vande Velde, C., Cizeau, J., Park, J. H., et al. (2000) BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites. J. Biol. Chem. 275, 1439-1448 https://doi.org/10.1074/jbc.275.2.1439
  40. Regula, K. M., Ens, K., and Kirshenbaum, L. A. (2002) Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ. Res. 91, 226−231 https://doi.org/10.1161/01.RES.0000026600.67226.92
  41. Sandau, K. B., Fandrey, J., and Brune, B. (2001) Accumulation of HIF-1alpha under the influence of nitric oxide. Blood 97, 1009−1015 https://doi.org/10.1182/blood.V97.1.1
  42. Sowter, H. M., Ratcliffe, P. J., Watson, P., Greenberg, A. H., and Harris, A. L. (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res. 61, 6669−6673
  43. Sowter, H. M., Ferguson, M., Pym, C., Watson, P., Fox, S. B., et al. (2003) Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade. J. Pathol. 201, 573−580 https://doi.org/10.1002/path.1433
  44. Turpaev, K., Bouton, C., Diet, A., Glatigny, A., and Drapier, J. C. (2005) Analysis of differentially expressed genes in nitric oxide-exposed human monocytic cells. Free Radic. Biol. Med. 38, 1392−1400 https://doi.org/10.1016/j.freeradbiomed.2005.02.002
  45. Vande Velde, C., Cizeau, J., Dubik, D., Alimonti, J., Brown, T., et al. (2000) BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol. Cell. Biol. 20, 5454−5468
  46. Wan, J., Martinvalet, D., Ji, X., Lois, C., Kaech, S. M., et al. (2003) The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytes. Immunology 110, 10−17 https://doi.org/10.1046/j.1365-2567.2003.01710.x
  47. Webster, K. A., Graham, R. M., and Bishopric, N. H. (2005) BNip3 and signal-specific programmed death in the heart. J. Mol. Cell. Cardiol. 38, 35−45 https://doi.org/10.1016/j.yjmcc.2004.11.007
  48. Yamashita, S., Tsujino, Y., Moriguchi, K., Tatematsu, M., and Ushijima, T. (2006) Chemical genomic screening for methylation- silenced genes in gastric cancer cell lines using 5-aza- 2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 97, 64−71 https://doi.org/10.1111/j.1349-7006.2005.00134.x
  49. Yasuda, M., Theodorakis, P., Subramanian, T., and Chinnadurai, G. (1998) Adenovirus E1B-19K/BCL-2 interacting protein BNIP3 contains a BH3 domain and a mitochondrial targeting sequence. J. Biol. Chem. 273, 12415−12421 https://doi.org/10.1074/jbc.273.1.1
  50. Yook, Y. H., Kang, K. H., Maeng, O., Kim, T. R., Lee, J. O., et al. (2004) Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem. Biophys. Res. Commun. 321, 298−305 https://doi.org/10.1016/j.bbrc.2004.06.093