BFAR

Last update 08 May 2025

Basic Info

Synonyms

BAR, BFAR, bifunctional apoptosis regulator

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Introduction

Membrane-bound E3 ubiquitin ligase that plays a role in several processes including apoptosis regulation or reticulum endoplasmic stress (PubMed:14502241, PubMed:21068390). Has anti-apoptotic activity, both for apoptosis triggered via death-receptors and via mitochondrial factors (PubMed:14502241). Contributes to the dynamic control of IRE1/ERN1 signaling during ER stress by inducing BAX inhibitor 1/TMBIM6 proteasomal degradation (PubMed:21068390). Promotes the activation of TGF-beta signaling by mediating the 'Lys-63'-linked ubiquitination of TGFBR1 which is critical to activate the pathway (PubMed:33914044). Together with NGFR, negatively regulates NF-kappa-B and JNK-related signaling pathways (PubMed:22566094). Promotes the proteasome-mediated degradation of PNPLA3, a protein involveld in lipid metabolism (PubMed:38294943).

100 Clinical Results associated with BFAR

100 Translational Medicine associated with BFAR

0 Patents (Medical) associated with BFAR

Literatures (Medical) associated with BFAR

06 Feb 2024·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

The ubiquitin E3 ligase BFAR promotes degradation of PNPLA3

Q1 · CROSS-FIELD

Article

Author: Das, Avash ; Cheng, Haili ; Kinch, Lisa N. ; Hong, Sen ; Cohen, Jonathan C. ; Liang, Guosheng ; Hobbs, Helen H. ; Wang, Yang

A missense variant in patatin-like phospholipase domain-containing protein 3 [PNPLA3(I148M)] is the most impactful genetic risk factor for fatty liver disease (FLD). We previously showed that PNPLA3 is ubiquitylated and subsequently degraded by proteasomes and autophagosomes and that the PNPLA3(148M) variant interferes with this process. To define the machinery responsible for PNPLA3 turnover, we used small interfering (si)RNAs to inactivate components of the ubiquitin proteasome system. Inactivation of bifunctional apoptosis regulator (BFAR), a membrane-bound E3 ubiquitin ligase, reproducibly increased PNPLA3 levels in two lines of cultured hepatocytes. Conversely, overexpression of BFAR decreased levels of endogenous PNPLA3 in HuH7 cells. BFAR and PNPLA3 co-immunoprecipitated when co-expressed in cells. BFAR promoted ubiquitylation of PNPLA3 in vitro in a reconstitution assay using purified, epitope-tagged recombinant proteins. To confirm that BFAR targets PNPLA3, we inactivatedBfarin mice. Levels of PNPLA3 protein were increased twofold in hepatic lipid droplets ofBfar−/−mice with no associated increase in PNPLA3 mRNA levels. Taken together these data are consistent with a model in which BFAR plays a role in the post-translational degradation of PNPLA3. The identification of BFAR provides a potential target to enhance PNPLA3 turnover and prevent FLD.

01 Oct 2023·Apoptosis : an international journal on programmed cell death

Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway.

Article

Author: Ding, Xiaoyan ; Liu, Guoxiang ; Sun, Hongxiao ; Li, Bing ; Chen, Guang ; Dong, Xiaolei ; Yang, Lina ; Zhu, Yunfan ; Feng, Guilin ; Wang, Yafei ; Yang, Fanghao ; Wang, Xiaotong ; Zhang, Huhu

Gastric cancer (GC) is the most common malignant tumor of digestive system. Bufalin extracted from Venenum Bufonis is one of the most effective anticancer monomers, which has been proved to play anticancer roles in a variety of cancers such as ovarian cancer, prostate cancer and neuroblastoma. However, there are few studies on bufalin in GC, and lack of clear targets. The effect of bufalin on the proliferation and migration of GC cells was detected by CCK-8, scratch wound healing assay, transwell assay and Western blotting. The potential direct interaction proteins of bufalin were screened by human proteome microarray containing 21,838 human proteins. The target protein was determined by bioinformatics, and the binding sites were predicted by molecular docking technique. Biological experiments in vitro and in vivo were conducted to verify the effect of bufalin directly interaction protein and the mechanism of bufalin targeting the protein to inhibit the development of GC. The results showed that bufalin inhibited the proliferation and migration of MKN-45 and HGC-27 GC cell lines in vitro. BFAR, a direct interaction protein of bufalin has several potential binding sites to bufalin. BFAR is highly expressed in GC and promotes the occurrence and metastasis of GC by activating PI3K/AKT/mTOR signal pathway in vitro and in vivo. Bufalin reversed the promoting effect of BFAR on the carcinogenesis and metastasis of GC by down-regulating the expression of BFAR. Our results show that bufalin targeting BFAR inhibits the occurrence and metastasis of GC through PI3K/AKT/mTOR signal pathway. These results provide a new basis for bufalin as a promising drug for the treatment of GC.

01 Sep 2021·Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchQ3 · BIOLOGY

The periphilin 1-like BFAR isoform 3 is highly expressed in transcriptionally silent oocytes and involved in RNA metabolism

Q3 · BIOLOGY

Article

Author: Pietrowska, Monika ; Widłak, Wiesława ; Chadalski, Marek ; Mrowiec, Katarzyna ; Paszek, Anna ; Toma-Jonik, Agnieszka ; Janus, Patryk ; Vydra, Natalia ; Gramatyka, Michalina

The mouse 3110001I22Rik gene located in the first intron of Bfar is considered as a Bfar variant coding for the BFARv3 protein. However, it differs from other BFAR isoforms and resembles periphilin 1 (PPHLN1) due to its two (Lge1 and serine-rich) conserved domains. We identified the BFARv3/EGFP-interacting proteins by co-immunoprecipitation coupled to mass spectrometry, which revealed 40S ribosomal proteins (RPS3, RPS14, RPS19, RPS25, RPS27), histones (H1.2, H1.4, H3.3C), proteins involved in RNA processing and splicing (SFPQ, SNRPA1, HNRNPA3, NONO, KHDRBS3), calcium signaling (HPCAL1, PTK2B), as well as HSD17B4, GRB14, POSTN, and MYO10. Co-immunoprecipitation revealed that both Lge1 and Ser-rich domains of BFARv3 were necessary for binding to RNA-interacting factors NONO and SFPQ, known to be components of paraspeckles. Reciprocal co-immunoprecipitation and the proximity ligation assay confirmed that both BFARv3 and PPHLN1 could interact with NONO and SFPQ, suggesting a new function for PPHLN1 as well. BFARv3 and its Lge1 or Ser-rich-deficient mutants preferentially localize in the nucleus. We found an accumulation of BFARv3/EGFP (but not its mutated forms) in the nuclear granules, which was enhanced in response to arsenite treatment and ionizing radiation. Although Bfar v3 is expressed ubiquitously in mouse tissues, its expression is the highest in metaphase II oocytes. The BFARv3 interactome suggests its role in RNA metabolism, which is critical for the transcriptionally silent MII oocyte. Mouse BFARv3 has no ortholog in the human genome, thus it may contribute to the differences between these two species observed in oocyte maturation and early embryonic development.

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