title: The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a novel apoptosis-inducing sequence.
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.
authors.affiliation: Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, The National University of Singapore, Blk S2, 14 Science Drive 4, Singapore 117543, Republic of Singapore.
authors.forename: Yi Ting
authors.initials: YT
authors.lastname: Zhou
authors.forename: Unice J K
authors.initials: UJ
authors.lastname: Soh
authors.forename: Xun
authors.initials: X
authors.lastname: Shang
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Guy
authors.forename: Boon Chuan
authors.initials: BC
authors.lastname: Low
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D049294:Phospholipid Transfer Proteins; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry*
chemical_list: D017304:Annexin A5; C499184:BNIP2 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D018076:DNA, Complementary; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D001616:beta-Galactosidase; D020764:cdc42 GTP-Binding Protein