apoptosis regulator Bcl-2; B-cell CLL/lymphoma-2 (bcl-2) protein (BCL2)
Jump to navigation
Jump to search
Function
- suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic & neural cells
- Bcl-2 prevents apoptosis triggered by various death stimuli including growth factor deprivation, radiation, cytotoxic chemotherapy, & in some cases Fas activation
- cytotoxic T-cell mediated apoptosis is resistant to bcl-2[5]
- regulates cell death by controlling mitochondrial membrane permeability
- appears to function in a feedback loop system with caspases
- inhibits caspase activity either by preventing the release of cytochrome c from mitochondria &/or by binding to the apoptosis-activating factor (APAF1)
- forms homodimers, & heterodimers with BAX, BAD, BAK & Bcl-X(L)
- heterodimerization with BAX requires intact BH1 & BH2 motifs, & is necessary for anti-apoptotic activity
- also interacts with APAF1, RAF-1, TP53BP2, BBC3, BCL2L1, MRPL41 & BNIPL
- binding to FKBP8 seems to target BCL2 to the mitochondria & probably interferes with binding of BCL2 to its targets
- phosphorylation/dephosphorylation on Ser-70 regulates anti- apoptotic activity
- growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity & occurs during the G2/M phase of the cell cycle
- in the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs & stress-activated kinases
- dephosphorylated by protein phosphatase 2A (PP2A) (putative)
- 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
Structure
- BH4 motif is required for anti-apoptotic activity & for interaction with RAF-1
- belongs to the Bcl-2 family
Compartment
- mitochondrial outer membrane
- nucleus membrane
- endoplasmic reticulum membrane
Alternative splicing
named isoforms=2; alpha; beta
Expression
expressed in a variety of tissues
Pathology
- breakpoint translocation t(14,18)[8] involving BCL2 may be a cause of follicular lymphoma
- translocation t(14;18)(q32;q21) involving BCL2 with immunoglobulin gene regions are found in non-Hodgkin lymphomas
Laboratory
More general terms
- proto oncogene protein
- bcl-2 subfamily protein
- mitochondrial membrane protein
- nuclear protein
- oligomerizing protein
- anti apoptotic protein
Additional terms
References
- ↑ Hockenbery D et al Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2250705
- ↑ Martin SJ, Green DR, Cotter TG. Dicing with death: dissecting the components of the apoptosis machinery. Trends Biochem Sci. 1994 Jan;19(1):26-30. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8140617
- ↑ Yin XM, Oltvai ZN, Korsmeyer SJ. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994 May 26;369(6478):321-3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8183370
- ↑ Lacronique V, Mignon A, Fabre M, Viollet B, Rouquet N, Molina T, Porteu A, Henrion A, Bouscary D, Varlet P, Joulin V, Kahn A. Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice. Nat Med. 1996 Jan;2(1):80-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8564847
- ↑ 5.0 5.1 Kumar S. ICE-like proteases in apoptosis. Trends Biochem Sci. 1995 May;20(5):198-202. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7610484
- ↑ Korsmeyer SJ. Regulators of cell death. Trends Genet. 1995 Mar;11(3):101-5. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7732571
- ↑ Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001 Jan;26(1):61-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11165519
- ↑ 8.0 8.1 Tsujimoto et al. Science 228:1440-3, 1985
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=596
- ↑ UniProt http://www.uniprot.org/uniprot/P10415.html
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/BCL2ID49.html
- ↑ NIEHS-SNPs http://egp.gs.washington.edu/data/bcl2/
- ↑ Wikipedia; Note: Bcl-2 entry Shttp://en.wikipedia.org/wiki/Bcl-2
Database
- UniProt: http://www.uniprot.org/uniprot/P10415.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=596
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:596
- OMIM: https://mirror.omim.org/entry/151430
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?