Disease relevance of BNIP1

• BNIP1, a member of the BH3-only protein family, was first discovered as one of the proteins that are capable of interacting with the antiapoptotic adenovirus E1B 19-kDa protein [1].
• The expression of the DNA repair protein human O(6)-alkylguanine-DNA alkyltransferase (AGT) in Escherichia coli strains GWR109 or TRG8 that lack endogenous AGT greatly increased the toxicity and mutagenicity of 1,2-dibromoethane (DBE) [2].

High impact information on BNIP1

• We have isolated cDNAs for three different proteins, designated Nip1, Nip2, and Nip3, that interact with the 19 kDa protein [3].
• Here we disclose a totally unexpected finding that BNIP1 is a component of the complex comprising syntaxin 18, an endoplasmic reticulum (ER)-located soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) [1].
• Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion [1].
• When the cells were rendered permeable to BG by mutating the lipopolysaccharide membrane component forming strain TRG8, the protection by AGT expression was abolished by treating the cells with BG [4].
• The sequence coding for PVP at positions 138-140 in AGT was replaced with a random nucleotide sequence, and this library was used to transform TRG8 [4].

Biological context of BNIP1

• The BNIP1 gene has been assigned to chromosome 5q33-34 [5].
• This predicts that alpha-SNAP may suppress apoptosis by competing with antiapoptotic proteins for the BH3 domain of BNIP1 [1].

Associations of BNIP1 with chemical compounds

• The results suggest that the BNIP1 variants are novel members of the BCL2 family but function through a mechanism different from other BH3-only members [5].

Physical interactions of BNIP1

• Using in vitro protein-protein interaction assays, all BNIP1 variants were shown to interact with BCL2 and also with BCL2L1 (previously Bcl-xL) [5].

Other interactions of BNIP1

• The TM domains of BNIP3 and BNIP1 can functionally substitute for the TM domain of a BCL-2 family member EBV-BHRF1 [6].
• Furthermore, the BNIP1 variants cannot interact with BAX [5].

Analytical, diagnostic and therapeutic context of BNIP1

• By PCR and EST database searches we have identified three novel BNIP1 splice variants, and found that one of them, BNIP1-b, contains a highly conserved BH3 domain [5].

References