title: MBP-1 mediated apoptosis involves cytochrome c release from mitochondria.
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.
authors.affiliation: Department of Pathology, Saint Louis University, St. Louis, Missouri, MO 63104, USA.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Mainak
authors.initials: M
authors.lastname: Majumder
authors.forename: Robert
authors.initials: R
authors.lastname: Steele
authors.forename: Ta-Jen
authors.initials: TJ
authors.lastname: Liu
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; C063232:HIVEP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases