MBP-1 mediated apoptosis involves cytochrome c release from mitochondria

Asish K. Ghosh, Mainak Majumder, Robert Steele, Ta J. Liu, Ratna B. Ray

Research output: Contribution to journalArticle

21 Scopus citations

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 adenovirns (d1312) 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 d1312 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 downregnlating 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.

Original languageEnglish (US)
Pages (from-to)2775-2784
Number of pages10
JournalOncogene
Volume21
Issue number18
DOIs
StatePublished - Apr 25 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-x
  • Cytochrome c
  • MBP-1

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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  • Cite this

    Ghosh, A. K., Majumder, M., Steele, R., Liu, T. J., & Ray, R. B. (2002). MBP-1 mediated apoptosis involves cytochrome c release from mitochondria. Oncogene, 21(18), 2775-2784. https://doi.org/10.1038/sj/onc/1205384