| Background |
Bif-1/SH3GLB1/Endophilin-B1 is a member of the endophilin B family that was originally identified as a Bax binding protein through yeast two-hybrid screening Bif-1 does not have significant homology to other Bcl-2 family members, but rather contains an N-terminal Bin-Amphiphysin-Rvs (BAR) domain, typically involved in membrane dynamics, and a C-terminal SH3 domain. Overexpression of Bif-1 promotes Bax conformational change and apoptosis Likewise, loss of Bif-1 inhibits Bax and Bak activation, cytochrome c release, and caspase activation Bif-1 is localized to membranes of intracellular organelles and has been suggested to play a role in membrane dynamics, including that during autophagy. Bif-1 directly binds to UVRAG, forming a complex with Beclin-1, resulting in increased PI3-kinase class III/Vps34 activity required for autophagosome maturation Inhibition of GSK-3β, as seen during nutrient deprivation, results in increased expression of Bif-1, and can contribute to autophagic cell death Research studies have shown that loss of Bif-1 promotes tumorigenesis, and decreased expression of Bif-1 has been noted in several cancer types.
|