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MBP-1 mediated apoptosis involves cytochrome c release from mitochondria

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Abstract

MBP-1, a cellular factor, appears to be involved in multiple functions, including transcriptional modulation, apoptosis and cell growth regulation. In this study, we have investigated the signaling pathway involved in MBP-1 mediated apoptotic cell death. Human carcinoma cells infected with a replication deficient adenovirus expressing MBP-1 (AdMBP-1) induced apoptosis, when compared with cells infected by replication-defective adenovirus (dl312) as a negative control. Transduction of MBP-1 in carcinoma cells releases cytochrome c from mitochondria into the cytosol leading to activation of procaspase-9, procaspase-3 and PARP cleavage. We previously observed that MBP-1 mediated apoptosis can be protected by Bcl-2, although MBP-1 does not share a homology with the BH domain of the Bcl-2 family member of proteins. To further understand the mechanism of MBP-1 mediated apoptosis, we examined whether MBP-1 modulates the Bcl-2 gene family. Our results demonstrated that human breast carcinoma cells infected with AdMBP-1 selectively reduced Bcl-xL mRNA and protein expression when compared with dl312 infected negative control cells. An in vitro transient reporter assay also suggested repression of the Bcl-x promoter activity by MBP-1. Additional studies indicated that MBP-1 modulates Ets family protein function, thereby downregulating Bcl-xL expression. Taken together, our results suggest that MBP-1 selectively represses Bcl-xL expression in MCF-7 cells and induces mitochondrial involvement in the apoptotic process.

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References

  • Ackermann EJ, Taylor JK, Narayana R, Bennett CF . 1999 J. Biol. Chem. 274: 11245–11252

  • Adams JM, Cory S . 1998 Science 281: 1322–1326

  • Antonsson B, Martinou JC . 2000 Exp. Cell Res. 256: 50–57

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB . 1993 Cell 74: 597–608

  • Bossy-Wetzel E, Newmeyer DD, Green DR . 1998 EMBO J. 17: 37–49

  • Cai J, Yang J, Jones DP . 1998 Biochim. Biophys. Acta. 1366: 139–149

  • Chaudhury D, Miller DM . 1995 Biochemistry 34: 3438–3445

  • Chao DT, Korsmeyer SJ . 1998 Annu. Rev. Immunol. 16: 395–419

  • Chen HM, Boxer LM . 1995 Mol. Cell. Biol. 15: 3840–3847

  • Ealovega MW, McGinnis PK, Sumantran VN, Clarke MF, Wicha MS . 1996 Cancer Res. 56: 1965–1969

  • Feo S, Arcuri D, Piddini E, Passantino R, Giallongo A . 2000 FEBS Lett. 473: 47–52

  • Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS, Poirier GG . 1999 J. Biol. Chem. 274: 28379–28384

  • Ghosh AK, Steele R, Ray RB . 1999 Mol. Cell. Biol. 19: 2880–2886

  • Ghosh AK, Majumder M, Steele R, Yaciuk P, Chrivia J, Ray R, Ray RB . 2000 J. Biol. Chem. 275: 7184–7188

  • Ghosh AK, Majumder M, Steele R, White RA, Ray RB . 2001 Mol. Cell. Biol. 21: 655–662

  • Giallongo A, Feo S, Moore R, Croce CM, Showe LC . 1986 Proc. Natl. Acad. Sci. USA 83: 6741–6745

  • Graham FL . 2000 Immunol. Today 21: 426–428

  • Green DR, Reed JC . 1998 Science 281: 1309–1312

  • Grillot DA, Gonzalez-Garcia M, Ekhterae D, Duan L, Inohara N, Ohta S, Seldin MF, Nunez Z . 1997 J. Immunol. 158: 4750–4757

  • Hatano E, Bradham CA, Stark A, Iimuro Y, Lemasters JJ, Brenner DA . 2000 J. Biol. Chem. 275: 11814–11823

  • Hu Y, Benedict MA, Wu D, Inohara N, Nunez G . 1998 Proc. Natl. Acad. Sci. USA 95: 4386–4391

  • Kharbanda S, Pandey P, Schofield L, Israels S, Roncinske R, Yoshida K, Bharti A, Yuan ZM, Saxena S, Weichselbaum R, Nalin C, Kufe D . 1997 Proc. Natl. Acad. Sci. USA 94: 6939–6942

  • Kim TH, Zhao Y, Barber MJ, Kuharsky DK, Yin XM . 2000 J. Biol. Chem. 275: 39474–39481

  • Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD . 1997 Science 275: 1132–1136

  • Li F, Srinivasan A, Wang Y, Armstrong RC, Tomaselli KJ, Fritz LC . 1997 J. Biol. Chem. 272: 30299–30305

  • Liu R, Page C, Beidler DR, Wicha MS, Nunez G . 1999a Am. J. Pathol. 155: 1861–1867

  • Liu T-J, El-Naggar AK, McDonnell TJ, Steck KD, Wang M, Taylor DL, Clayman GL . 1995 Cancer Res. 55: 3117–3122

  • Liu T-J, Wang M, Breau RL, Henderson Y, El-Naggar AK, Steck KD, Sicard MW, Clayman GL . 1999b Cancer Gene Ther. 6: 163–172

  • Liu X, Kim CN, Yang J, Jemmerson R, Wang X . 1996 Cell 86: 147–157

  • Mercatante DR, Bortner CD, Cidlowski JA, Kole R . 2001 J. Biol. Chem. 276: 16411–16417

  • Olopade OI, Adeyanju MO, Safa AR, Hagos F, Mick R, Thompson CB, Recant WM . 1997 Cancer J. Sci. Am. 3: 230–237

  • Ray RB . 1995 Cell Growth Differ. 6: 1089–1096

  • Ray RB, Meyer K, Steele R, Shrivastava A, Aggarwal BB, Ray R . 1998 J. Biol. Chem. 273: 2256–2259

  • Ray R, Miller DM . 1991 Mol. Cell. Biol. 11: 2154–2161

  • Ray RB, Sheikh MS, Fontana JF, Miller DM . 1994 Int. J. Oncol. 5: 1433–1436

  • Ray RB, Steele R, Seftor E, Hendrix M . 1995 Cancer Res. 55: 3747–3751

  • Ray R, Thomas S, Miller DM . 1989 Oncogene 4: 593–600

  • Reed JC . 1997 Cell 91: 559–562

  • Reed JC . 1998 Cancer J. Sci. Am. 4: S8–S14

  • Reed JC . 1999 J. Clin. Oncol. 17: 2941–2953

  • Reed JC, Jurgensmeier JM, Matsuyama S . 1998 Biochim. Biophys. Acta 1366: 127–137

  • Reeve JG, Xiong J, Morgan J, Bleehen NM . 1996 Br. J. Cancer 73: 1193–1200

  • Schmitt E, Cimoli G, Steyaert A, Bertrand R . 1998 Exp. Cell Res. 240: 107–121

  • Sevilla L, Aperlo C, Dulic V, Chambard JC, Boutonnet C, Pasquier O, Pognonec P, Boulukos KE . 1999 Mol. Cell. Biol. 19: 2624–2634

  • Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y . 1996 Oncogene 13: 21–29

  • Shi Y, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP, Green DR . 1992 Science 257: 212–214

  • Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang H-G, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ . 1999 J. Cell Biol. 144: 281–292

  • Steller H . 1995 Science 267: 1445–1449

  • Strasser A, O'Connor L, Dixit VM . 2000 Annu. Rev. Biochem. 69: 217–245

  • Subramaniun A, Miller DM . 2000 J. Biol. Chem. 275: 5958–5965

  • Susin SA, Zamzami N, Kroemer G . 1998 Biochim. Biophys. Acta 1366: 151–165

  • Thompson CB . 1995 Science 267: 1456–1462

  • Thornberry NA, Lazebnik Y . 1998 Science 281: 1312–1326

  • Tu Y, Renner S, Xu F, Fleishman A, Taylor J, Weisz J, Vescio R, Rettig M, Berenson J, Krajewski S, Reed JC, Lichtenstein A . 1998 Cancer Res. 58: 256–262

  • White RA, Adkison LR, Dowler LL, Ray RB . 1997 Genomics 39: 406–408

  • Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X . 1997 Science 275: 1129–1132

  • Yasushi F, Keita K, Hisao H, Keiko Y-T, Tadamitsu K . 1997 J. Clin. Invest. 99: 2898–2905

  • Zamzami N, Brenner C, Marzo I, Susin SA, Kroemer G . 1998 Oncogene 16: 2265–2282

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Acknowledgements

This research was supported by grant CA52799 from the National Cancer Institute. We thank Linda Boxer, G Chinnadurai and Ranjan Sen for helpful suggestions. Authors thank G Chinnadurai for providing Bcl-2 antibody, Keiko Yamauchi-Takihara for providing Bcl-x promoter constructs, and Maria Trojanowska for providing synthetic Ets-TK construct and Ets-1 cDNA for our research.

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Authors and Affiliations

  1. Department of Pathology, Saint Louis University, St. Louis, Missouri, 63104, MO, USA

    Asish K Ghosh, Mainak Majumder, Robert Steele & Ratna B Ray

  2. Division of Infectious Diseases, Saint Louis University, St. Louis, Missouri, 63104, MO, USA

    Ratna B Ray

  3. Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Ta-Jen Liu

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  1. Asish K Ghosh
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  2. Mainak Majumder
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Correspondence to Ratna B Ray.

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Ghosh, A., Majumder, M., Steele, R. et al. MBP-1 mediated apoptosis involves cytochrome c release from mitochondria. Oncogene 21, 2775–2784 (2002). https://doi.org/10.1038/sj.onc.1205384

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