BCL2
GeneName
BCL2
Summary
BCL2, also known as Bcl-2, is a 26kDa anti-apoptotic protein predominantly localised to the mitochondrial outer membrane, endoplasmic reticulum, and nuclear membrane. It plays a critical role in regulating apoptosis by inhibiting the release of cytochrome c from mitochondria, thus preventing the activation of caspases and promoting cell survival. BCL2 is involved in various biological processes, including B cell homeostasis, T cell differentiation, and cellular responses to stressors such as hypoxia and oxidative stress. It interacts with several proteins through its BH3 domain and is implicated in multiple signalling pathways that govern cell fate decisions.
Importance
BCL2 is relevant to: - Cancer research due to its role in preventing apoptosis, contributing to tumourigenesis and resistance to therapy - Autoimmune diseases where dysregulation of apoptosis can lead to abnormal immune responses - Neurodegenerative disorders, as its expression can influence neuronal survival and death - Developmental biology, given its involvement in processes like B cell and T cell maturation and differentiation.
Top Products
For researchers investigating BCL2, we highly recommend the top-selling recombinant antibody, Anti-Bcl-2 antibody [E17] (ab32124). This well-cited product boasts an impressive 1648 citations, underscoring its reliability and trust within the scientific community. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), and immunoprecipitation (IP). This versatility makes it an excellent choice for those seeking consistent and effective detection of BCL2 in their experiments. The Human Bcl-2 ELISA Kit (ab272102), supported by 4 citations, is an excellent option for researchers looking to accurately measure Bcl-2 levels in their samples.
Abcam Product Citation Summary
The data indicates a significant focus on the role of BCL2 in various contexts related to apoptosis, cancer, and cellular responses to stress. The use of Abcam antibodies in studies involving human and mouse models highlights the importance of BCL2 in understanding tumor growth, metastasis, and the mechanisms of cell death. The diverse applications of these antibodies in Western blotting and flow cytometry across multiple cell types and conditions suggest that BCL2 is a critical target for research in cancer biology and therapeutic interventions.
Abcam Product Citation Table
Domain
BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.
The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.
The BH3 domain is required for interaction with SEPTIN4 isoform ARTS and thereby for XIAP-mediated ubiquitination and subsequent induction of apoptosis.
Function
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells (PubMed:1508712, PubMed:8183370). Regulates cell death by controlling the mitochondrial membrane permeability (PubMed:11368354). Appears to function in a feedback loop system with caspases (PubMed:11368354). Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) (PubMed:11368354). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function (PubMed:18570871, PubMed:20889974, PubMed:21358617). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
Involvement in disease
A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
Post-translational modifications
Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity (PubMed:11368354). Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle (PubMed:11368354). In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases (PubMed:11368354). Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, which stimulates starvation-induced autophagy (PubMed:10567572, PubMed:18570871). Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).
Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.
Monoubiquitinated by PRKN, leading to an increase in its stability (PubMed:20889974). Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome (PubMed:23431138). Ubiquitinated by XIAP, leading to its degradation by the proteasome (PubMed:29020630).
Sequence Similarities
Belongs to the Bcl-2 family.
Tissue Specificity
Expressed in a variety of tissues.
Cellular localization
- Mitochondrion outer membrane
- Single-pass membrane protein
- Nucleus membrane
- Single-pass membrane protein
- Endoplasmic reticulum membrane
- Single-pass membrane protein
- Cytoplasm
Alternative names
Apoptosis regulator Bcl-2, BCL2