1. The BNIP-2 and Cdc42GAP Homology/Sec14p-like Domain of BNIP-Sα Is a Novel Apoptosis-inducing Sequence
- Author
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Graeme R. Guy, Unice J. K. Soh, Yi Ting Zhou, Boon Chuan Low, and Xun Shang
- Subjects
DNA, Complementary ,Time Factors ,Recombinant Fusion Proteins ,Amino Acid Motifs ,Blotting, Western ,Molecular Sequence Data ,Apoptosis ,Biology ,Biochemistry ,Homology (biology) ,Mice ,Tumor Cells, Cultured ,Animals ,Humans ,Protein Isoforms ,Tissue Distribution ,Amino Acid Sequence ,Annexin A5 ,Cloning, Molecular ,Phospholipid Transfer Proteins ,cdc42 GTP-Binding Protein ,Molecular Biology ,Gene ,Peptide sequence ,Glutathione Transferase ,Cell Nucleus ,Microscopy, Confocal ,Base Sequence ,Cell Death ,Sequence Homology, Amino Acid ,Reverse Transcriptase Polymerase Chain Reaction ,Alternative splicing ,Intron ,Membrane Proteins ,Cell Biology ,beta-Galactosidase ,Molecular biology ,Chromatin ,Protein Structure, Tertiary ,Alternative Splicing ,Microscopy, Fluorescence ,Cdc42 GTP-Binding Protein ,RNA splicing ,Carrier Proteins ,Sequence motif ,Protein Binding ,Signal Transduction - Abstract
We have cloned the cDNAs for two novel human proteins, designated BNIP-Salpha and beta (for BNIP-2 Similar) that are homologous to BNIP-2, a previously known Bcl-2 and E1B-associated protein. The BNIP-S gene encodes two protein isoforms; the longer protein (BNIP-Salpha) contains a complete BNIP-2 and Cdc42GAP Homology (BCH) domain, a novel protein domain that we recently identified, whereas its shorter variant (BNIP-Sbeta) lacks the full BCH domain as a result of an alternative RNA splicing that introduces a nonsense intron. Primer-specific reverse-transcription PCR revealed that both BNIP-Salpha and BNIP-Sbeta mRNA are differentially expressed in various cells and tissues. The expression of BNIP-Salpha or the complete BCH domain, but not BNIP-Sbeta, causes extensive apoptosis in cells. Furthermore, BNIP-Salpha can form a homophilic complex via a unique sequence motif within its BCH domain, and deletion of this interacting motif prevents its pro-apoptotic effect. These results indicate the presence of two BNIP-S splicing variants as cellular regulators and that the BCH domain of BNIP-Salpha confers a novel apoptotic function. The significance of this is discussed.
- Published
- 2002
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