BMRP is a Bcl-2 binding protein that induces apoptosis.
Members of the Bcl-2 family of proteins play important roles in the regulation of cell death by apoptosis. The yeast Two-Hybrid system was utilized to identify a protein that interacts with the anti-apoptotic protein Bcl-2, designated BMRP. This protein corresponds to a previously known mitochondrial ribosomal protein (MRPL41). Binding experiments confirmed the interaction of BMRP to Bcl-2 in mammalian cells. Subcellular fractionation by differential centrifugation studies showed that both Bcl-2 and BMRP are localized to the same fractions (fractions that are rich in mitochondria). Northern blot analysis revealed a major bmrp mRNA band of approximately 0.8 kb in several human tissues. Additionally, a larger 2.2 kb mRNA species was also observed in some tissues. Western blot analysis showed that endogenous BMRP runs as a band of 16-17 kDa in SDS-PAGE. Overexpression of BMRP induced cell death in primary embryonic fibroblasts and NIH/3T3 cells. Transfection of BMRP showed similar effects to those observed by overexpression of the pro-apoptotic proteins Bax or Bad. BMRP-stimulated cell death was counteracted by co-expression of Bcl-2. The baculoviral caspase inhibitor p35 also protected cells from BMRP-induced cell death. These findings suggest that BMRP is a mitochondrial ribosomal protein involved in the regulation of cell death by apoptosis, probably affecting pathways mediated by Bcl-2 and caspases.
Chintharlapalli
Sudhakar R
SR
Departments of Biology and Chemistry, Texas A&M University-Kingsville, 700 University Blvd., Kingsville, Texas 78363, USA.
Jasti
Madhuri
M
Malladi
Srinivas
S
Parsa
Kishore V L
KV
Ballestero
Rafael P
RP
González-García
Maribel
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; C502654:MRPL41 protein, human; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012269:Ribosomal Proteins