p75NTR signal transduction suppressed by BFAR and p75NTR interactions
- Sci China Life Sci. 2012 Apr;55(4):367-74. doi: 10.1007/s11427-012-4306-y.
- 1. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
p75NTR is a low-affinity nerve growth factor receptor, which promotes cell proliferation as a positive modulator of high-affinity receptor TrkA, as well as binds with cell ligands to induce Apoptosis and mediate death signals. To analyze the regulatory mechanisms of p75NTR, the present study utilized a new membrane yeast two-hybrid system to screen a human fetal brain cDNA library. Results identified BFAR, a novel protein that interacts with p75NTR. Interaction specificity was verified by membrane yeast two-hybrid co-transformation assays, in vitro GST pull-down assays, and in vitro co-immunoprecipitation assays. The fluorescent subcellular localization assay revealed that the two proteins co-localized within the cytoplasm. BFAR overexpression in PC-12 and HEK293T cells inhibited the NFκB and JNK signaling pathway, as determined with the luciferase test. Co-transfected p75NTR and BFAR in HEK293T or PC-12 cells, respectively, increased the percentage of cells in the G2/M phase, decreased the number of S-phase cells, and did not change the number of G0/G1-phase cells.