Apoptosis Database

Description [+]

Synonyms: PMAIP1, PHORBOL-12-MYRISTATE-13-ACETATE-INDUCED PROTEIN 1, NOXA, ZGC:162379
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Pisces; Danio rerio
Short gene description: phorbol-12-myristate-13-acetate-induced protein 1 [Source:RefSeq_peptide;Acc:NP_001038939]
Family: Bcl-2 family : BH3-only
Process: apoptosis,
Pathways: intrinsic pathway, pre-mitochondrial signaling events,
Criteria: manually curated
Curator comment: Ectopic expression of Pmaip1 in zebrafish embryos induces apoptosis [ Ref: 16888646 , Ref: 18404156 "> Ref: Ref: 18404156 ]. The BH3 domain peptide from zebrafish Pmaip1 induces cytochrome c release in mitochondria isolated from mouse embryonic fibroblasts (MEFs) [ Ref: 18404156 "> Ref: Ref: 18404156 ].
WIKI: PMAIP1-D_rerio

References [+]

Functional characterization of the Bcl-2 gene family in the zebrafish.
Kratz E, Eimon PM, Mukhyala K, Stern H, Zha J, Strasser A, Hart R, Ashkenazi A
Members of the Bcl-2 protein family control the intrinsic apoptosis pathway. To evaluate the importance of this family in vertebrate development, we investigated it in the zebrafish (Danio rerio). We found that the zebrafish genome encodes structural and functional homologs of most mammalian Bcl-2 family members, including multi-Bcl-2-homology (BH) domain proteins and BH3-only proteins. Apoptosis induction by gamma-irradiation required zBax1 and zPuma, and could be prevented by overexpression of homologs of prosurvival Bcl-2 family members. Surprisingly, zebrafish Bax2 (zBax2) was homologous to mammalian Bax by sequence and synteny, yet demonstrated functional conservation with human Bak. Morpholino knockdown of both zMcl-1a and zMcl-1b revealed their critical role in early embryonic zebrafish development, and in the modulation of apoptosis activation through the extrinsic pathway. These data indicate substantial functional similarity between zebrafish and mammalian Bcl-2 family members, and establish the zebrafish as a relevant model for studying the intrinsic apoptosis pathway. Cell Death Differ. 2006 Oct;13(10):1631-40. Epub 2006 Aug 4.

BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals.
Jette CA, Flanagan AM, Ryan J, Pyati UJ, Carbonneau S, Stewart RA, Langenau DM, Look AT, Letai A
Here we investigate the function of zebrafish Bcl-2 family proteins and demonstrate important conservation of function across zebrafish and mammalian systems. We have isolated a zebrafish ortholog of mammalian BIM and show that it is the most toxic of the zebrafish BH3-only genes examined, sharing this characteristic with the mammalian BIM gene. The zebrafish bad gene shows a complete lack of embryonic lethality, but like mammalian BAD, its pro-apoptotic activity is regulated through phosphorylation of critical serines. We also found that the pattern of mitochondrial dysfunction observed by zebrafish BH3 domain peptides in a mammalian cytochrome c release assay recapitulates the pattern of embryonic lethality induced by the respective mRNA injections in vivo. In contrast to zebrafish Bim, Bid exhibited only weak binding to zebrafish Bcl-2 and moderate-to-weak overall lethality in zebrafish embryos and isolated mitochondria. Given that zebrafish Bcl-2 binds strongly to mammalian BID and BIM peptides and proteins, the protein identified as the zebrafish Bid ortholog has different properties than mammalian BID. Overall, our results demonstrate the high degree of functional conservation between zebrafish and mammalian Bcl-2 family proteins, thus validating the zebrafish as a model system to further dissect the molecular mechanisms that regulate apoptosis in future forward genetic and chemical modifier screens. Cell Death Differ. 2008 Jun;15(6):1063-72. Epub 2008 Apr 11.

Structure & Sequence [+]

Evolution [+]

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0043065	positive regulation of apoptosis	biological_proccess	IDA
GO:0003674	molecular_function	mollecular_function	ND
GO:0005575	cellular_component	cell_component	ND

KEGG Pathways [+]

Information from other databases [+]

PMAIP1 (Danio rerio)