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Bcl-2

 
Sci-Tech Dictionary: bcl-2
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(biochemistry) A family of proteins that operate in the effector phase of apoptosis and may either promote or inhibit apoptosis.

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Wikipedia: Bcl-2
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B-cell CLL/lymphoma 2
BCL2 Crystal Structure.rsh.png
PDB rendering based on 1G5M.
Available structures
2o2f
Identifiers
Symbols BCL2; Bcl-2
External IDs OMIM: 151430 MGI: 88138 HomoloGene: 527
RNA expression pattern
PBB GE BCL2 203685 at tn.png
PBB GE BCL2 203684 s at tn.png
PBB GE BCL2 207005 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 596 12043
Ensembl ENSG00000171791 ENSMUSG00000057329
UniProt P10415 Q4VBF6
RefSeq NM_000633 (mRNA) NM_009741 (mRNA)
NP_000624 (protein) NP_033871 (protein)
Location Chr 18:
58.94 - 59.14 Mb		 Chr 1:
108.37 - 108.54 Mb
PubMed search [1] [2]

Bcl-2 is the prototype for a family of mammalian genes and the proteins they produce. They govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro-apoptotic (Bax, BAD, Bak and Bok among others) or anti-apoptotic (including Bcl-2 proper, Bcl-xL, and Bcl-w, among an assortment of others). There are a total of 25 genes in the Bcl-2 family known to date. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described as a reciprocal gene translocation in chromosomes 14 and 18 in follicular lymphomas.

Contents

Function

There are a number of theories concerning how the Bcl-2 gene family exert their pro- or anti-apoptotic effect. An important one states that this is achieved by activation or inactivation of an inner mitochondrial permeability transition pore, which is involved in the regulation of matrix Ca2+, pH, and voltage. It is also thought that some Bcl-2 family proteins can induce (pro-apoptotic members) or inhibit (anti-apoptotic members) the release of cytochrome c into the cytosol which, once there, activates caspase-9 and caspase-3, leading to apoptosis. Although Zamzami et al. suggest that the release of cytochrome c is indirectly mediated by the PT pore on the inner mitochondrial membrane,[1] strong evidence suggest an earlier implication of the MAC pore on the outer membrane.[2][3]

Bcl-2 family[4]

Another theory suggests that Rho proteins play a role in Bcl-2, Mcl-1 and Bid activation. Rho inhibition reduces the expression of anti-apoptotic Bcl-2 and Mcl-1 proteins and increases protein levels of pro-apoptotic Bid but had no effect on Bax or FLIP levels. Rho inhibition induces caspase-9 and caspase-3-dependent apoptosis of cultured human endothelial cells.[5]

The members of the Bcl-2 family share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4) (see the figure on the left). The BH domains are known to be crucial for function, as deletion of these domains via molecular cloning affects survival/apoptosis rates. The anti-apoptotic Bcl-2 proteins, such as Bcl-2 and Bcl-xL, conserve all four BH domains. The BH domains also serve to subdivide the pro-apoptotic Bcl-2 proteins into those with several BH domains (e.g. Bax and Bak) or those proteins that have only the BH3 domain (e.g. Bid, Bim and Bad). The Bcl-2 family has a general structure that consists of a hydrophobic helix surrounded by amphipathic helices. Many members of the family have transmembrane domains. The site of action for the Bcl-2 family is mostly on the outer mitochondrial membrane. Within the mitochondria are apoptogenic factors (cytochrome c, Smac/DIABLO, Omi) that if released activate the executioners of apoptosis, the caspases.[6] Depending on their function, once activated, Bcl-2 proteins either promote the release of these factors, or keep them sequestered in the mitochondria. Whereas the activated pro-apoptotic Bak and/or Bax would form MAC and mediate the release of cytochrome c, the anti-apoptotic Bcl-2 would block it, possibly through inhibition of Bax and/or Bak.[7]

Role in disease

The Bcl-2 gene has been implicated in a number of cancers, including melanoma, breast, prostate, and lung carcinomas, as well as schizophrenia and autoimmunity. It is also thought to be involved in resistance to conventional cancer treatment. This supports a role for decreased apoptosis in the pathogenesis of cancer.

Cancer is one of the world's leading causes of death and occurs when the homeostatic balance between cell growth and death is disturbed. Research in cancer biology has discovered that a variety of aberrations in gene expression of anti-apoptotic, pro-apoptotic and BH3-only proteins can contribute to the many forms of the disease. An interesting example can be seen in lymphomas. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone did not act in an oncogenic manner. But simultaneous overexpression of Bcl-2 and the protooncogene myc may produce aggressive B-cell malignancies including lymphoma.[8] In follicular lymphoma, a chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes—t(14;18)—which places the Bcl-2 gene next to the immunoglobulin heavy chain locus. This fusion gene is deregulated, leading to the transcription of excessively high levels of bcl-2.[9] This decreases the propensity of these cells for undergoing apoptosis.

Apoptosis also plays a very active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. "In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases.[10] The autoimmune disease, type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells (DCs) are of the most important antigen presenting cells of the immune system, their activity must be tightly regulated by such mechanisms as apoptosis. "Researchers have found that mice containing DCs that are Bim -/-, thus unable to induce effective apoptosis, obtain autoimmune diseases more so than those that have normal DCs.[10] Other studies have shown that the lifespan of DCs may be controlled by factors such as a timer dependent on anti-apoptotic Bcl-2.[10] These investigations illuminate the importance of regulating antigen presentation as mis-regulation can lead to autoimmunity.

Apoptosis plays a very important role in regulating a variety of diseases that have enormous social impacts. For example, schizophrenia is a neurodegenerative disease that may result from an abnormal ratio of pro- and anti-apoptotic factors.[11] There is some evidence that this defective apoptosis may result from abnormal expression of Bcl-2 and increased expression of caspase-3.[11]

Further research into the family of Bcl-2 proteins will provide a more complete picture on how these proteins interact with each other to promote and inhibit apoptosis. An understanding of the mechanisms involved will help discover potential treatments such as inhibitors to target over-expressed proteins that may lead to new therapies in cancer, autoimmune conditions, and neurological diseases.

Targeted therapies

An antisense oligonucleotide drug Genasense (G3139) has been developed to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA which hybridises with and inactivates mRNA, preventing the protein from being formed.

It was shown that the proliferation of human lymphoma cells (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.[12]

These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial is currently underway[13]

Genasense did not receive FDA approval after disappointing results in a melanoma trial.

Abbott has recently described a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737.[14] ABT-737 is one among many so-called BH3 mimetic small molecule inhibitors (SMI) targeting Bcl-2 and Bcl-2-related proteins such as Bcl-xL and Bcl-w but not A1 and Mcl-1, which may prove valuable in the therapy of lymphoma and other blood cancers.[15]

BH3-only family

BH3-only family of proteins includes those of the Bcl-2 family proteins, which contain only a single BH-domain. The BH3-only family members play a key role in promoting apoptosis. The BH3-only family members are BAD, Bim and others. Various apoptotoc stimuli induce expression and/or activation of specific BH3-only family members, which translocate to the mitochondria and initiate Bax/Bak-dependent apoptosis.[16]

Interactions

Overview of signal transduction pathways involved in apoptosis.

Bcl-2 has been shown to interact with RAD9A,[17] BAK1,[18][19] Reticulon 4,[20] Bcl-2-associated X protein,[21][18][22][17] Caspase 8,[23][24] BECN1,[25] SOD1,[26] Bcl-2-interacting killer,[27][28] BH3 interacting domain death agonist,[27][29] RRAS,[30] C-Raf,[31] BCL2L11,[27][32][33] BNIPL,[34][35] HRK,[27][36] PSEN1,[37] BMF,[38] BNIP2,[34][39] BNIP3,[39][40] Nerve Growth factor IB,[18] BCL2-like 1,[41][18] Myc,[42] BCAP31,[43] SMN1,[44] CAPN2,[45] PPP2CA,[46] Noxa,[27][47] Cdk1,[48][49] TP53BP2,[50] Bcl-2-associated death promoter[27][51] and IRS1.[52]

Human BCL-2 genes

BAK; BAK1; BAX; BCL2; BCL2A1; BCL2L1; BCL2L10; BCL2L13; BCL2L14; BCL2L2; BCL2L7P1; BOK; MCL1;

See also

References

  1. ^ Zamzami N, Brenner C, Marzo I, Susin SA, Kroemer G (April 1998). "Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins". Oncogene 16 (17): 2265–82. doi:10.1038/sj.onc.1201989. PMID 9619836. 
  2. ^ Kinnally KW, Antonsson B (May 2007). "A tale of two mitochondrial channels, MAC and PTP, in apoptosis". Apoptosis 12 (5): 857–68. doi:10.1007/s10495-007-0722-z. PMID 17294079. 
  3. ^ Martinez-Caballero S, Dejean LM, Jonas EA, Kinnally KW (June 2005). "The role of the mitochondrial apoptosis induced channel MAC in cytochrome c release". J. Bioenerg. Biomembr. 37 (3): 155–64. doi:10.1007/s10863-005-6570-z. PMID 16167172. 
  4. ^ Chao DT, Korsmeyer SJ (1998). "BCL-2 family: regulators of cell death". Annu. Rev. Immunol. 16: 395–419. doi:10.1146/annurev.immunol.16.1.395. PMID 9597135. 
  5. ^ Hippenstiel S, Schmeck B, N'Guessan PD, Seybold J, Krüll M, Preissner K, Eichel-Streiber CV, Suttorp N (October 2002). "Rho protein inactivation induced apoptosis of cultured human endothelial cells". Am. J. Physiol. Lung Cell Mol. Physiol. 283 (4): L830–8. doi:10.1152/ajplung.00467.2001. PMID 12225960. 
  6. ^ Fesik SW, Shi Y. (2001). "Controlling the caspases". Science 294 (5546): 1477. doi:10.1126/science.1062236. PMID 11711663. 
  7. ^ Dejean LM, Martinez-Caballero S, Manon S, Kinnally KW (February 2006). "Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins". Biochim. Biophys. Acta 1762 (2): 191–201. doi:10.1016/j.bbadis.2005.07.002. PMID 16055309. 
  8. ^ Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Pineda-Roman M, Stuart RK, Spicer EK, Fernandes DJ (April 2007). "Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA". Blood 109 (7): 3069–75. doi:10.1182/blood-2006-08-043257. PMID 17179226. 
  9. ^ Vaux DL, Cory S, Adams JM (September 1988). "Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells". Nature 335 (6189): 440–2. doi:10.1038/335440a0. PMID 3262202. 
  10. ^ a b c Li A, Ojogho O, Escher A (2006). "Saving death: apoptosis for intervention in transplantation and autoimmunity". Clin. Dev. Immunol. 13 (2-4): 273–82. doi:10.1080/17402520600834704. PMID 17162368. 
  11. ^ a b Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF (January 2006). "Apoptotic mechanisms and the synaptic pathology of schizophrenia". Schizophr. Res. 81 (1): 47–63. doi:10.1016/j.schres.2005.08.014. PMID 16226876. 
  12. ^ Dias N, Stein CA (November 2002). "Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". Eur J Pharm Biopharm 54 (3): 263–9. doi:10.1016/S0939-6411(02)00060-7. PMID 12445555. http://linkinghub.elsevier.com/retrieve/pii/S0939641102000607. 
  13. ^ Mavromatis BH, Cheson BD (June 2004). "Novel therapies for chronic lymphocytic leukemia". Blood Rev. 18 (2): 137–48. doi:10.1016/S0268-960X(03)00039-0. PMID 15010151. 
  14. ^ Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH (June 2005). "An inhibitor of Bcl-2 family proteins induces regression of solid tumours". Nature 435 (7042): 677–81. doi:10.1038/nature03579. PMID 15902208. 
  15. ^ Reed JC, Pellecchia M (July 2005). "Apoptosis-based therapies for hematologic malignancies". Blood 106 (2): 408–18. doi:10.1182/blood-2004-07-2761. PMID 15797997. 
  16. ^ Michael Kastan; Abeloff, Martin D.; Armitage, James O.; Niederhuber, John E. (2008). Abeloff's clinical oncology (4th ed.). Philadelphia: Churchill Livingstone/Elsevier. ISBN 0-443-06694-9. 
  17. ^ a b Komatsu, K; Miyashita T, Hang H, Hopkins K M, Zheng W, Cuddeback S, Yamada M, Lieberman H B, Wang H G (Jan. 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nat. Cell Biol. (ENGLAND) 2 (1): 1-6. doi:10.1038/71316. ISSN 1465-7392. PMID 10620812. 
  18. ^ a b c d Lin, Bingzhen; Kolluri Siva Kumar, Lin Feng, Liu Wen, Han Young-Hoon, Cao Xihua, Dawson Marcia I, Reed John C, Zhang Xiao-kun (Feb. 2004). "Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3". Cell (United States) 116 (4): 527-40. ISSN 0092-8674. PMID 14980220. 
  19. ^ Enyedy, I J; Ling Y, Nacro K, Tomita Y, Wu X, Cao Y, Guo R, Li B, Zhu X, Huang Y, Long Y Q, Roller P P, Yang D, Wang S (Dec. 2001). "Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening". J. Med. Chem. (United States) 44 (25): 4313-24. ISSN 0022-2623. PMID 11728179. 
  20. ^ Tagami, S; Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov. 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene (England) 19 (50): 5736-46. doi:10.1038/sj.onc.1203948. ISSN 0950-9232. PMID 11126360. 
  21. ^ Hoetelmans, R W M (Jun. 2004). "Nuclear partners of Bcl-2: Bax and PML". DNA Cell Biol. (United States) 23 (6): 351-4. doi:10.1089/104454904323145236. ISSN 1044-5498. PMID 15231068. 
  22. ^ Oltvai, Z N; Milliman C L, Korsmeyer S J (Aug. 1993). "Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death". Cell (UNITED STATES) 74 (4): 609-19. ISSN 0092-8674. PMID 8358790. 
  23. ^ Poulaki, V; Mitsiades N, Romero M E, Tsokos M (Jun. 2001). "Fas-mediated apoptosis in neuroblastoma requires mitochondrial activation and is inhibited by FLICE inhibitor protein and Bcl-2". Cancer Res. (United States) 61 (12): 4864-72. ISSN 0008-5472. PMID 11406564. 
  24. ^ Guo, Yin; Srinivasula Srinivasa M, Druilhe Anne, Fernandes-Alnemri Teresa, Alnemri Emad S (Apr. 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. (United States) 277 (16): 13430-7. doi:10.1074/jbc.M108029200. ISSN 0021-9258. PMID 11832478. 
  25. ^ Liang, X H; Kleeman L K, Jiang H H, Gordon G, Goldman J E, Berry G, Herman B, Levine B (Nov. 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". J. Virol. (UNITED STATES) 72 (11): 8586-96. ISSN 0022-538X. PMID 9765397. 
  26. ^ Pasinelli, Piera; Belford Mary Elizabeth, Lennon Niall, Bacskai Brian J, Hyman Bradley T, Trotti Davide, Brown Robert H (Jul. 2004). "Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria". Neuron (United States) 43 (1): 19-30. doi:10.1016/j.neuron.2004.06.021. ISSN 0896-6273. PMID 15233914. 
  27. ^ a b c d e f Chen, Lin; Willis Simon N, Wei Andrew, Smith Brian J, Fletcher Jamie I, Hinds Mark G, Colman Peter M, Day Catherine L, Adams Jerry M, Huang David C S (Feb. 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell (United States) 17 (3): 393-403. doi:10.1016/j.molcel.2004.12.030. ISSN 1097-2765. PMID 15694340. 
  28. ^ Gillissen, Bernhard; Essmann Frank, Graupner Vilma, Stärck Lilian, Radetzki Silke, Dörken Bernd, Schulze-Osthoff Klaus, Daniel Peter T (Jul. 2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". EMBO J. (England) 22 (14): 3580-90. doi:10.1093/emboj/cdg343. ISSN 0261-4189. PMID 12853473. 
  29. ^ Real, Pedro Jose; Cao Yeyu, Wang Renxiao, Nikolovska-Coleska Zaneta, Sanz-Ortiz Jaime, Wang Shaomeng, Fernandez-Luna Jose Luis (Nov. 2004). "Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2". Cancer Res. (United States) 64 (21): 7947-53. doi:10.1158/0008-5472.CAN-04-0945. ISSN 0008-5472. PMID 15520201. 
  30. ^ Fernandez-Sarabia, M J; Bischoff J R (Nov. 1993). "Bcl-2 associates with the ras-related protein R-ras p23". Nature (ENGLAND) 366 (6452): 274-5. doi:10.1038/366274a0. ISSN 0028-0836. PMID 8232588. 
  31. ^ Wang, H G; Rapp U R, Reed J C (Nov. 1996). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell (UNITED STATES) 87 (4): 629-38. ISSN 0092-8674. PMID 8929527. 
  32. ^ O'Connor, L; Strasser A, O'Reilly L A, Hausmann G, Adams J M, Cory S, Huang D C (Jan. 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis". EMBO J. (ENGLAND) 17 (2): 384-95. doi:10.1093/emboj/17.2.384. ISSN 0261-4189. PMID 9430630. 
  33. ^ Hsu, S Y; Lin P, Hsueh A J (Sep. 1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members". Mol. Endocrinol. (UNITED STATES) 12 (9): 1432-40. ISSN 0888-8809. PMID 9731710. 
  34. ^ a b Qin, Wenxin; Hu Jian, Guo Minglei, Xu Jian, Li Jinjun, Yao Genfu, Zhou Xiaomei, Jiang Huiqiu, Zhang Pingping, Shen Li, Wan Dafang, Gu Jianren (Aug. 2003). "BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis". Biochem. Biophys. Res. Commun. (United States) 308 (2): 379-85. ISSN 0006-291X. PMID 12901880. 
  35. ^ Yasuda, M; Han J W, Dionne C A, Boyd J M, Chinnadurai G (Feb. 1999). "BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3". Cancer Res. (UNITED STATES) 59 (3): 533-7. ISSN 0008-5472. PMID 9973195. 
  36. ^ Inohara, N; Ding L, Chen S, Núñez G (Apr. 1997). "harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". EMBO J. (ENGLAND) 16 (7): 1686-94. doi:10.1093/emboj/16.7.1686. ISSN 0261-4189. PMID 9130713. 
  37. ^ Alberici, A; Moratto D, Benussi L, Gasparini L, Ghidoni R, Gatta L B, Finazzi D, Frisoni G B, Trabucchi M, Growdon J H, Nitsch R M, Binetti G (Oct. 1999). "Presenilin 1 protein directly interacts with Bcl-2". J. Biol. Chem. (UNITED STATES) 274 (43): 30764-9. ISSN 0021-9258. PMID 10521466. 
  38. ^ Puthalakath, H; Villunger A, O'Reilly L A, Beaumont J G, Coultas L, Cheney R E, Huang D C, Strasser A (Sep. 2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science (United States) 293 (5536): 1829-32. doi:10.1126/science.1062257. ISSN 0036-8075. PMID 11546862. 
  39. ^ a b Boyd, J M; Malstrom S, Subramanian T, Venkatesh L K, Schaeper U, Elangovan B, D'Sa-Eipper C, Chinnadurai G (Oct. 1994). "Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins". Cell (UNITED STATES) 79 (2): 341-51. ISSN 0092-8674. PMID 8001138. 
  40. ^ Ray, R; Chen G, Vande Velde C, Cizeau J, Park J H, Reed J C, Gietz R D, Greenberg A H (Jan. 2000). "BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites". J. Biol. Chem. (UNITED STATES) 275 (2): 1439-48. ISSN 0021-9258. PMID 10625696. 
  41. ^ Zhang, Haichao; Nimmer Paul, Rosenberg Saul H, Ng Shi-Chung, Joseph Mary (Aug. 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Anal. Biochem. (United States) 307 (1): 70-5. ISSN 0003-2697. PMID 12137781. 
  42. ^ Jin, Zhaohui; Gao Fengqin, Flagg Tammy, Deng Xingming (Sep. 2004). "Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. Biol. Chem. (United States) 279 (38): 40209-19. doi:10.1074/jbc.M404056200. ISSN 0021-9258. PMID 15210690. 
  43. ^ Ng, F W; Nguyen M, Kwan T, Branton P E, Nicholson D W, Cromlish J A, Shore G C (Oct. 1997). "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". J. Cell Biol. (UNITED STATES) 139 (2): 327-38. ISSN 0021-9525. PMID 9334338. 
  44. ^ Iwahashi, H; Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (Nov. 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature (ENGLAND) 390 (6658): 413-7. doi:10.1038/37144. ISSN 0028-0836. PMID 9389483. 
  45. ^ Gil-Parrado, Shirley; Fernández-Montalván Amaury, Assfalg-Machleidt Irmgard, Popp Oliver, Bestvater Felix, Holloschi Andreas, Knoch Tobias A, Auerswald Ennes A, Welsh Katherine, Reed John C, Fritz Hans, Fuentes-Prior Pablo, Spiess Eberhard, Salvesen Guy S, Machleidt Werner (Jul. 2002). "Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members". J. Biol. Chem. (United States) 277 (30): 27217-26. doi:10.1074/jbc.M202945200. ISSN 0021-9258. PMID 12000759. 
  46. ^ Deng, X; Ito T, Carr B, Mumby M, May W S (Dec. 1998). "Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A". J. Biol. Chem. (UNITED STATES) 273 (51): 34157-63. ISSN 0021-9258. PMID 9852076. 
  47. ^ Oda, E; Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (May. 2000). "Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis". Science (UNITED STATES) 288 (5468): 1053-8. ISSN 0036-8075. PMID 10807576. 
  48. ^ Pathan, N; Aime-Sempe C, Kitada S, Basu A, Haldar S, Reed J C. "Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1". Neoplasia (United States) 3 (6): 550-9. doi:10.1038/sj/neo/7900213. ISSN 1522-8002. PMID 11774038. 
  49. ^ Pathan, N; Aime-Sempe C, Kitada S, Haldar S, Reed J C. "Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with Pin1". Neoplasia (United States) 3 (1): 70-9. doi:10.1038/sj/neo/7900131. ISSN 1522-8002. PMID 11326318. 
  50. ^ Naumovski, L; Cleary M L (Jul. 1996). "The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M". Mol. Cell. Biol. (UNITED STATES) 16 (7): 3884-92. ISSN 0270-7306. PMID 8668206. 
  51. ^ Yang, E; Zha J, Jockel J, Boise L H, Thompson C B, Korsmeyer S J (Jan. 1995). "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death". Cell (UNITED STATES) 80 (2): 285-91. ISSN 0092-8674. PMID 7834748. 
  52. ^ Ueno, H; Kondo E, Yamamoto-Honda R, Tobe K, Nakamoto T, Sasaki K, Mitani K, Furusaka A, Tanaka T, Tsujimoto Y, Kadowaki T, Hirai H (Feb. 2000). "Association of insulin receptor substrate proteins with Bcl-2 and their effects on its phosphorylation and antiapoptotic function". Mol. Biol. Cell (UNITED STATES) 11 (2): 735-46. ISSN 1059-1524. PMID 10679027. 

External links

v • d • e
Neoplasm: Oncogenes/Proto-oncogenes
Extracellular/
Growth factor
Cell membrane/
receptor/tyrosine kinases
Cytoplasm/
Signal transduction
Nucleus/Transcription factors
Other/ungrouped
c-Bcl-2 - Notch - Stathmin
v • d • e
Apoptosis signaling pathway
Fas
Membrane
Intracellular
TNF
Membrane
Intracellular
TRADD

FADD · Caspase 8 · Caspase 3 · BID

TRAF2 · ASK-1 · MEKK1 · IKK · IκBα · MKK7 · JNK · NF-κB
Other
XIAP · NAIP · Survivin · c-IAP-1 · c-IAP-2

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