The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a novel apoptosis-inducing sequence.
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.
Zhou
Yi Ting
YT
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.
Soh
Unice J K
UJ
Shang
Xun
X
Guy
Graeme R
GR
Low
Boon Chuan
BC
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*
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