Technical Data
B0083-11
BFAR (Bifunctional Apoptosis Regulator, RING Finger Protein 47, BAR, RNF47)
Description:
BAR (bifunctional apoptosis regulator) is a multidomain protein that was originally identified as an inhibitor of Bax-induced apoptosis (Zhang et al, 2000). Apoptosis induction can be divided up into two major pathways, extrinsic and intrinsic. The extrinsic pathway is represented by death receptor signaling and the intrinsic pathway depends on mitochondrial events. BAR is in anchored in intracellular membranes and is thought to be a scaffold protein that may bridge components of both extrinsic and intrinsic apoptosis pathways through its antiapoptotic domains: 1. BAR contains a DED (death effector domain)-like protein interaction domain that suppresses death receptor apoptosis signaling pathways. Death receptors such as the TNF (tumor necrosis factor)-family contain protein interaction domains called DD (death domains) in their cytosolic regions. DD-containing TNF receptor family members such as Fas aggregate upon binding ligand and bind to an adaptor protein FADD which contains both DD and DED domains. The Fas/FADD complexes bind to the caspase family members such as 8 and 10 which contain DEDs in their N-terminal prodomain. This is followed by proteolytic processing and caspase activation, thereby initiating a signal transduction cascade leading to activation of downstream effector caspases, substrate cleavage, andultimate cell death. DED-containing antiapoptotic proteins like BAR function as transdominant apoptosis inhibitors by competing for binding to the DED domains of proapoptotic proteins like Fadd, caspase-8 and caspase-10, thereby preventing assembly of functional death-inducing complexes and hence activation of downstream apoptosis signaling cascades. 2. BAR also contains a domain that mediates interactions with Bcl-2 family proteins and that is required for suppression of Bax-induced cell death in yeast and mammalian cells. Although the physiological functions of BAR remain to be elucidated. BAR is highly expressed in the brain and expression patterns as well as functionalDta with neuronal cell lines suggest that BAR is involved in regulating neuronal survival (Roth et al. 2003). Additionally, subcellular localization studies indicate that BAR predominantly localizes to the endoplasmic reticulum (ER), irrespective of cell type. Bcl-2 family proteins also localize to the ER. There is important crosstalk between the ER and mitochondria in the execution of cell death. It is thought that both BAR and Bcl-2 proteins play a role in regulating cell death/apoptosis induced by ER stress. Dysregulation of ER homeostasis and apoptosis is thought to be involved in the pathogenesis of some human neuronal diseases, including Alzheimer's, Parkinson's, polyglutamine diseases, nueronal storage diseases, prion dieases, as well as acute neurodegeration from brain trauma (reviewed in Lindholm et al, 2006). Since BAR is normally widely expressed in the brain, it may have a cytoprotective function in helping neurons to survive for the entire lifetime of the organism by playing a central role in inhibiting ER initiated apoptosis.

Applications:
Suitable for use in Western Blot, Immunohistochemistry and Immunoprecipitation. Other applications not tested.

Recommended Dilution:
Western Blot: 1:1000-1:2000
Immunohistochemistry (formalin fixed paraffin embedded): 1:1000-1:5000
Immunoprecipitation: 1:50-1:200
Immunohistochemistry: Frozen
Optimal dilutions to be determined by the researcher.

Positive Control:
CNS, neuronal cell lines

Storage and Stability:
May be stored at 4C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
TypeIsotypeCloneGrade
PabIgGSerum
SizeStorageShippingSourceHost
50ul-20CBlue IceHumanRabbit
Concentration:
Not determined
Immunogen:
Synthetic peptide corresponding to aa3-21 (EPQKSYVNTMDLERDEPLK) of human BAR; GenBank no. NP_057645.1.
Purity:
Serum
Form
Supplied as a liquid, 0.05% sodium azide.
Specificity:
Recognizes human BFAR.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.
1. Zhang H, Q Xu, S Krajewski, M Krajewska, Z Xie, S Fuess, S Kitada, K Pawlowski, A Godzik, and JC Reed. 2000. BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins. PNAS 97:2597-2602. 2. Roth W, P Kermer, M Krajewska, K Welsh, S Davis, S Krajewski, and JC Reed. 2003. Bifunctional apoptosis inhibitor (BAR) protects neurons from diverse cell death pathways. Cell Death Differentiation. 10:1178-1187. 3. Lindholm D, H Wootz, and L Korhonen. 2006. ER stress and neurodegenerative diseases. Cell Death Differentiation. 13:385-392.