p75NTR signal transduction suppressed by BFAR and p75NTR interactions

Abstract

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. p75NTR, BFAR, membrane yeast two-hybrid, protein-protein interaction, apoptosis

Hyperosmotic stress activates the expression of members of the miR-15/107 family and induces downregulation of anti-apoptotic genes in rat liver

“…9C , a total of 18 overlapping genes was identified (see also Table 1 ). Notably, three of the genes included in the list, namely the apoptosis antagonizing factor (Aatf), bifunctional apoptosis regulator (Bfar) and the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (Ikbkb) are known for their anti-apoptotic activity 34 35 36 37 38 . Importantly, the significant downregulation of Aatf, Bfar, Ikbkb and of other 12 predicted targets could be validated by using qPCR ( Fig.…”

“…Aatf ameliorates mitochondrial dysfunction by reducing oxidative damage 34 . Bfar is a multidomain protein that interacts with members of the extrinsic and intrinsic apoptosis pathways 35 and inhibits JNK signaling 36 . JNK signaling might thus be activated by downregulation of Bfar.…”

The p35/CDK5 signaling is regulated by p75NTR in neuronal apoptosis after intracerebral hemorrhage

“…In this study, the full‐length p75NTR tagged with flag N‐terminally as described by Li, Shi, and Huo (), was subcloned into p3xflag‐cmv‐13 and pEGFPc‐1 vectors to construct plasmids which contained C‐terminal flag‐tagged p75NTR (flag‐p75NTR). The HA‐tagged p35 (HA‐p35) plasmid was purchased from Ji Kai company (Shanghai, China).…”