From Wikipedia, the free encyclopedia
Jump to: navigation, search
B-cell CLL/lymphoma 2
BCL-2 human.png
PDB rendering based on 1GJH,1G5M.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols BCL2 ; Bcl-2; PPP1R50
External IDs OMIM151430 MGI88138 HomoloGene527 ChEMBL: 4860 GeneCards: BCL2 Gene
RNA expression pattern
PBB GE BCL2 203685 at.png
PBB GE BCL2 203684 s at.png
PBB GE BCL2 207005 s at.png
More reference expression data
Species Human Mouse
Entrez 596 12043
Ensembl ENSG00000171791 ENSMUSG00000057329
UniProt P10415 P10417
RefSeq (mRNA) NM_000633 NM_009741
RefSeq (protein) NP_000624 NP_033871
Location (UCSC) Chr 18:
63.12 – 63.32 Mb
Chr 1:
106.54 – 106.71 Mb
PubMed search [1] [2]

Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inducing (pro-apoptotic) or inhibiting (anti-apoptotic) apoptosis.[1][2] Bcl-2 is specifically considered an important anti-apoptotic protein and is thus classified as an oncogene.

Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs[3] (such as Bcl2 in mice) have been identified in numerous mammals for which complete genome data are available.

Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.


The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms [4]

Role in disease[edit]

Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and a possible cause of schizophrenia and autoimmunity. It is also a cause of resistance to cancer treatments.

(See also : Apoptosis#Implication_in_disease)


Cancer occurs as the result of a disturbance in the homeostatic balance between cell growth and cell death. Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. An example can be seen in lymphomas. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma.[5] In follicular lymphoma, a chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes — t(14;18) — which places the Bcl-2 gene from chromosome 18 next to the immunoglobulin heavy chain locus on chromosome 14. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2.[6] This decreases the propensity of these cells for undergoing apoptosis.

Auto-immune diseases[edit]

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.[7] 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 are 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 dendritic cells that are Bim -/-, thus unable to induce effective apoptosis, suffer autoimmune diseases more so than those that have normal dendritic cells.[7] Other studies have shown that the lifespan of dendritic cells may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.[7]


Apoptosis plays a very important role in regulating a variety of diseases. For example, schizophrenia is a neurodegenerative disease that may result from an abnormal ratio of pro- and anti-apoptotic factors.[8] There is some evidence that this defective apoptosis may result from abnormal expression of Bcl-2 and increased expression of caspase-3.[8]

Diagnostic use[edit]

Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen. In healthy tissue, these antibodies will react with B-cells in the mantle zone, as well as some T-cells. However, there is a considerable increase in positive cells in follicular lymphoma, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies may be significant for the patient's prognosis or likelihood of relapse.[9]

Targeted therapies[edit]

Bcl-2 inhibitors (many are BH3-mimetics) include :


An antisense oligonucleotide drug Genasense (G3139) has been developed by Genta Incorporated 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 that 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.[10]

These have shown successful results in Phase I/II trials for lymphoma, and a large Phase III trial was launched in 2004[11]

By the first quarter 2010, Genasense had not received FDA approval due to disappointing results in a melanoma trial. Although safety and efficacy of Genasense have not been established for any use, Genta Incorporated claimed on its website that studies were underway to examine the potential role of Genasense in a variety of clinical indications. In August 2012, Genta Incorporated shut down.

ABT-737, ABT-263[edit]

In the mid-2000s, Abbott Laboratories developed a novel inhibitor of Bcl-2, Bcl-xL, and Bcl-w, known as ABT-737. This compound is part of a group of BH3 mimetic small molecule inhibitors (SMI), which target these Bcl-2 family proteins, but not A1 or Mcl-1. ABT-737 is superior to previous BCL-2 inhibitors because this compound has higher affinity for Bcl-2, Bcl-xL, and Bcl-w. In in vitro studies, primary cells from patients with B-cell malignancies are extremely sensitive to ABT-737.[12] ABT-737 does not directly induce apoptosis; it enhances the effects of the death signals and causes single-agent-mechanism-based killing of cells in small-cell lung carcinoma and lymphoma lines. In animal models, it improves survival, causes tumor regression, and results in the cure of a high percentage of mice.[13] Finally, in preclinical studies utilizing patient xenografts, ABT-737 has shown efficacy for treating lymphoma and other blood cancers.[14] Because of its unfavorable pharmacologic properties ABT-737 is not appropriate for clinical trials, and its highly related derivative ABT-263 has similar activity on small cell lung cancer (SCLC) cell lines and has entered clinical trials.[15]


Clinical trials have studied the effects of venetoclax (ABT-199), a BH3-mimetic drug designed to block the function of the Bcl-2 protein, on patients with chronic lymphocytic leukemia.[16] Some very good responses have been reported.[17] After good results in phase 2 trials, a phase 3 trial is starting in Dec 2015.[18]



Overview of signal transduction pathways involved in apoptosis.

Bcl-2 has been shown to interact with:

Human BCL-2 genes[edit]

BAK; BAK1; BAX; BCL2; BCL2A1; BCL2L1; BCL2L10; BCL2L13; BCL2L14; BCL2L2; BCL2L7P1; BOK; MCL1; LGALS7 (Galectin-7)

See also[edit]


  1. ^ Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM (Nov 1984). "Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation". Science 226 (4678): 1097–9. doi:10.1126/science.6093263. PMID 6093263. 
  2. ^ Cleary ML, Smith SD, Sklar J (Oct 1986). "Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation". Cell 47 (1): 19–28. doi:10.1016/0092-8674(86)90362-4. PMID 2875799. 
  3. ^ "OrthoMaM phylogenetic marker: Bcl-2 coding sequence". 
  4. ^ "Human Bcl2, Isoform 1". 
  5. ^ Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Pineda-Roman M, Stuart RK, Spicer EK, Fernandes DJ (Apr 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. PMC 1852223. PMID 17179226. 
  6. ^ Vaux DL, Cory S, Adams JM (Sep 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. 
  7. ^ a b c Li A, Ojogho O, Escher A (2006). "Saving death: apoptosis for intervention in transplantation and autoimmunity". Clinical & Developmental Immunology 13 (2-4): 273–82. doi:10.1080/17402520600834704. PMC 2270759. PMID 17162368. 
  8. ^ a b Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF (Jan 2006). "Apoptotic mechanisms and the synaptic pathology of schizophrenia". Schizophrenia Research 81 (1): 47–63. doi:10.1016/j.schres.2005.08.014. PMID 16226876. 
  9. ^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. XX. ISBN 1-84110-100-1. 
  10. ^ Dias N, Stein CA (Nov 2002). "Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". European Journal of Pharmaceutics and Biopharmaceutics 54 (3): 263–9. doi:10.1016/S0939-6411(02)00060-7. PMID 12445555. 
  11. ^ Mavromatis BH, Cheson BD (Jun 2004). "Novel therapies for chronic lymphocytic leukemia". Blood Reviews 18 (2): 137–48. doi:10.1016/S0268-960X(03)00039-0. PMID 15010151. 
  12. ^ Vogler, Meike, et al. "Bcl-2 inhibitors: small molecules with a big impact on cancer therapy." Cell Death & Differentiation 16.3 (2008): 360-367.
  13. ^ Oltersdorf, Tilman, et al. "An inhibitor of Bcl-2 family proteins induces regression of solid tumours." Nature 435.7042 (2005): 677-681.
  14. ^ Hann, Christine L., et al. "Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer." Cancer research 68.7 (2008): 2321-2328.
  15. ^ Alterations in the Noxa/Mcl-1 axis determine sensitivity of small cell lung cancer to the BH3 mimetic ABT-737. Hauck. 2009
  16. ^ http://www.asianscientist.com/tech-pharma/abt-199-bh-3-mimetic-wehi-phase-ia-trial-chronic-lymphocytic-leukemia/
  17. ^ http://www.stokesentinel.co.uk/Miracle-drug-cured-cancer-Amazing-recovery/story-21080535-detail/story.html
  18. ^ Hard-to-Treat CLL Yields to Investigational Drug. ASH Dec 2015
  19. ^ http://www.genengnews.com/gen-news-highlights/cephalon-to-spend-225m-to-purchase-gemin-x-for-phase-ii-sclc-candidate/81244855/
  20. ^ a b c d Lin B, Kolluri SK, Lin F, Liu W, Han YH, Cao X, Dawson MI, Reed JC, Zhang XK (Feb 2004). "Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3". Cell 116 (4): 527–40. doi:10.1016/s0092-8674(04)00162-x. PMID 14980220. 
  21. ^ Enyedy IJ, Ling Y, Nacro K, Tomita Y, Wu X, Cao Y, Guo R, Li B, Zhu X, Huang Y, Long YQ, Roller PP, Yang D, Wang S (Dec 2001). "Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening". Journal of Medicinal Chemistry 44 (25): 4313–24. doi:10.1021/jm010016f. PMID 11728179. 
  22. ^ Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC (Oct 1997). "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". The Journal of Cell Biology 139 (2): 327–38. doi:10.1083/jcb.139.2.327. PMC 2139787. PMID 9334338. 
  23. ^ Zhang H, Nimmer P, Rosenberg SH, Ng SC, Joseph M (Aug 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Analytical Biochemistry 307 (1): 70–5. doi:10.1016/s0003-2697(02)00028-3. PMID 12137781. 
  24. ^ a b c d e f Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (Feb 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Molecular Cell 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340. 
  25. ^ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (Jan 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis". The EMBO Journal 17 (2): 384–95. doi:10.1093/emboj/17.2.384. PMC 1170389. PMID 9430630. 
  26. ^ Hsu SY, Lin P, Hsueh AJ (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". Molecular Endocrinology 12 (9): 1432–40. doi:10.1210/mend.12.9.0166. PMID 9731710. 
  27. ^ Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (Nov 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". Journal of Virology 72 (11): 8586–96. PMC 110269. PMID 9765397. 
  28. ^ Real PJ, Cao Y, Wang R, Nikolovska-Coleska Z, Sanz-Ortiz J, Wang S, Fernandez-Luna JL (Nov 2004). "Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2". Cancer Research 64 (21): 7947–53. doi:10.1158/0008-5472.CAN-04-0945. PMID 15520201. 
  29. ^ Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC, Strasser A (Sep 2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science 293 (5536): 1829–32. doi:10.1126/science.1062257. PMID 11546872. 
  30. ^ a b Qin W, Hu J, Guo M, Xu J, Li J, Yao G, Zhou X, Jiang H, Zhang P, Shen L, Wan D, Gu J (Aug 2003). "BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis". Biochemical and Biophysical Research Communications 308 (2): 379–85. doi:10.1016/s0006-291x(03)01387-1. PMID 12901880. 
  31. ^ a b Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, 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 79 (2): 341–51. doi:10.1016/0092-8674(94)90202-X. PMID 7954800. 
  32. ^ Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, Gietz RD, Greenberg AH (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". The Journal of Biological Chemistry 275 (2): 1439–48. doi:10.1074/jbc.275.2.1439. PMID 10625696. 
  33. ^ Yasuda M, Han JW, Dionne CA, Boyd JM, Chinnadurai G (Feb 1999). "BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3". Cancer Research 59 (3): 533–7. PMID 9973195. 
  34. ^ Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ (Jan 1995). "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death". Cell 80 (2): 285–91. doi:10.1016/0092-8674(95)90411-5. PMID 7834748. 
  35. ^ a b Komatsu K, Miyashita T, Hang H, Hopkins KM, Zheng W, Cuddeback S, Yamada M, Lieberman HB, Wang HG (Jan 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nature Cell Biology 2 (1): 1–6. doi:10.1038/71316. PMID 10620799. 
  36. ^ Hoetelmans RW (Jun 2004). "Nuclear partners of Bcl-2: Bax and PML". DNA and Cell Biology 23 (6): 351–4. doi:10.1089/104454904323145236. PMID 15231068. 
  37. ^ Oltvai ZN, Milliman CL, Korsmeyer SJ (Aug 1993). "Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death". Cell 74 (4): 609–19. doi:10.1016/0092-8674(93)90509-O. PMID 8358790. 
  38. ^ Gillissen B, Essmann F, Graupner V, Stärck L, Radetzki S, Dörken B, Schulze-Osthoff K, Daniel PT (Jul 2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". The EMBO Journal 22 (14): 3580–90. doi:10.1093/emboj/cdg343. PMC 165613. PMID 12853473. 
  39. ^ Wang HG, Rapp UR, Reed JC (Nov 1996). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell 87 (4): 629–38. doi:10.1016/s0092-8674(00)81383-5. PMID 8929532. 
  40. ^ Gil-Parrado S, Fernández-Montalván A, Assfalg-Machleidt I, Popp O, Bestvater F, Holloschi A, Knoch TA, Auerswald EA, Welsh K, Reed JC, Fritz H, Fuentes-Prior P, Spiess E, Salvesen GS, Machleidt W (Jul 2002). "Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members". The Journal of Biological Chemistry 277 (30): 27217–26. doi:10.1074/jbc.M202945200. PMID 12000759. 
  41. ^ Poulaki V, Mitsiades N, Romero ME, Tsokos M (Jun 2001). "Fas-mediated apoptosis in neuroblastoma requires mitochondrial activation and is inhibited by FLICE inhibitor protein and Bcl-2". Cancer Research 61 (12): 4864–72. PMID 11406564. 
  42. ^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (Apr 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". The Journal of Biological Chemistry 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478. 
  43. ^ Pathan N, Aime-Sempe C, Kitada S, Basu A, Haldar S, Reed JC. "Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1". Neoplasia 3 (6): 550–9. doi:10.1038/sj/neo/7900213. PMC 1506558. PMID 11774038. 
  44. ^ Pathan N, Aime-Sempe C, Kitada S, Haldar S, Reed JC. "Microtubule-targeting drugs induce Bcl-2 phosphorylation and association with Pin1". Neoplasia 3 (1): 70–9. doi:10.1038/sj/neo/7900131. PMC 1505024. PMID 11326318. 
  45. ^ 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)". The EMBO Journal 16 (7): 1686–94. doi:10.1093/emboj/16.7.1686. PMC 1169772. PMID 9130713. 
  46. ^ 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". Molecular Biology of the Cell 11 (2): 735–46. doi:10.1091/mbc.11.2.735. PMC 14806. PMID 10679027. 
  47. ^ Jin Z, Gao F, Flagg T, Deng X (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". The Journal of Biological Chemistry 279 (38): 40209–19. doi:10.1074/jbc.M404056200. PMID 15210690. 
  48. ^ 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 288 (5468): 1053–8. doi:10.1126/science.288.5468.1053. PMID 10807576. 
  49. ^ Deng X, Ito T, Carr B, Mumby M, May WS (Dec 1998). "Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1 is mediated by direct interaction with protein phosphatase 2A". The Journal of Biological Chemistry 273 (51): 34157–63. doi:10.1074/jbc.273.51.34157. PMID 9852076. 
  50. ^ Alberici A, Moratto D, Benussi L, Gasparini L, Ghidoni R, Gatta LB, Finazzi D, Frisoni GB, Trabucchi M, Growdon JH, Nitsch RM, Binetti G (Oct 1999). "Presenilin 1 protein directly interacts with Bcl-2". The Journal of Biological Chemistry 274 (43): 30764–9. doi:10.1074/jbc.274.43.30764. PMID 10521466. 
  51. ^ Fernandez-Sarabia MJ, Bischoff JR (Nov 1993). "Bcl-2 associates with the ras-related protein R-ras p23". Nature 366 (6452): 274–5. doi:10.1038/366274a0. PMID 8232588. 
  52. ^ 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 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360. 
  53. ^ 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 390 (6658): 413–7. doi:10.1038/37144. PMID 9389483. 
  54. ^ Pasinelli P, Belford ME, Lennon N, Bacskai BJ, Hyman BT, Trotti D, Brown RH (Jul 2004). "Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria". Neuron 43 (1): 19–30. doi:10.1016/j.neuron.2004.06.021. PMID 15233914. 
  55. ^ Naumovski L, Cleary ML (Jul 1996). "The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M". Molecular and Cellular Biology 16 (7): 3884–92. PMC 231385. PMID 8668206. 

External links[edit]