Abstract
We have previously reported on cloning of the human gene encoding Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-like protein (Bnip3L) and its growth inhibitory effect on cancer cells. Here we show that Bnip3L contains a motif similar to the BH3 domain which is conserved in Bcl-2 family proteins as well as containing a membrane-anchoring domain, and that Bnip3L interacts with Bcl-2 and Bcl-xL. Immunofluorescence microscopy revealed that Bnip3L was localized in the mitochondria, when in the presence of the membrane-anchoring domain. Transient expression of Bnip3L induced apoptosis of Rat-1 and HeLa cells and mutational analysis revealed that the BH3 domain and the membrane-anchoring domain were required for Bnip3L to induce cell death. Addition of recombinant Bnip3L to isolated mitochondria induced membrane potential loss and cytochrome c release both of which have been suggested to be prerequisite for apoptotic cell death. These results suggest that Bnip3L is one of the BH3-containing pro-apoptotic proteins and that it targets the mitochondria when inducing apoptosis.
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References
Adams JM and Cory S. . 1998 Science 281: 1322–1326.
Akao Y, Otsuki Y, Kataoka S, Ito Y and Tsujimoto Y. . 1994 Cancer Res. 54: 2468–2471.
Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D'Sa-Eipper C and Chinnadurai G. . 1994 Cell 79: 341–351.
Chen BG, Ray R, Dubik D, Shi L, Cizeau J, Bleackley RC, Saxena S, Gietz RD and Greenberg AH. . 1997 J. Exp. Med. 186: 1975–1983.
Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G and Lutz RJ. . 1995 EMBO J. 14: 5589–5596.
Conradt B and Horvitz HR. . 1998 Cell 93: 519–529.
Cosulich SC, Worrall V, Hedge PJ, Green S and Clarke PR. . 1997 Curr. Biol. 7: 913–920.
Green DR and Reed JC. . 1998 Science 281: 1309–1312.
Gross A, Jockel J, Wei MC and Korsmeyer SJ. . 1998 EMBO J. 17: 3878–3885.
Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D and Reed JC. . 1998 Proc. Natl. Acad. Sci. USA 95: 4997–5002.
Li H, Zhu H, Xu CJ and Yuan J. . 1998 Cell 94: 491–501.
Luo X, Budihardjo I, Zou H, Slaughter C and Wang X. . 1998 Cell 94: 481–490.
Matsushima M, Fujiwara T, Takahashi E, Minaguchi T, Eguchi Y, Tsujimoto Y, Suzumori K and Nakamura Y. . 1998 Genes Chrom. Cancer 21: 230–235.
Monaghan P, Robertson D, Amos TA, Dyer MJ, Mason DY and Greaves MF. . 1992 J. Histochem. Cytochem. 40: 1819–1825.
Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H and Tsujimoto Y. . 1998 Proc. Natl. Acad. Sci. USA 95: 14681–14686.
Niwa H, Yamamura K and Miyazaki J. . 1991 Gene 108: 193–199.
Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB and Fesik SW. . 1997 Science 275: 983–986.
Shimizu S, Eguchi Y, Kamiike W, Funahashi Y, Mignon A, Lacronique V, Matsuda H and Tsujimoto Y. . 1998 Proc. Natl. Acad. Sci. USA 95: 1455–1459.
Thompson CB. . 1995 Science 267: 1456–1462.
Yasuda M, Theodorakis P, Subramanian T and Chinnadurai G. . 1998a J. Biol. Chem. 273: 12415–12421.
Yasuda M, D'Sa-Eipper C, Gong X and Chinnadurai G. . 1998b Oncogene 17: 2525–2530.
Zha J, Harada H, Yang E, Jockel J and Korsmeyer SJ. . 1996 Cell 87: 619–628.
Acknowledgements
This study was supported in part by a grant for Scientific Research on Priority Areas, by a grant for Center of Excellence Research, and by a grant for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
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Imazu, T., Shimizu, S., Tagami, S. et al. Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability. Oncogene 18, 4523–4529 (1999). https://doi.org/10.1038/sj.onc.1202722
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DOI: https://doi.org/10.1038/sj.onc.1202722
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