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MBP-1 mediated apoptosis involves cytochrome c release from mitochondria

Oncogene volume 21, pages 2775–2784 (2002)Cite this article

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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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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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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