Bcl-2

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B-ćelijski CLL/limfom 2

PDB prikaz bazairan na 1GJH, 1G5M.
Dostupne strukture
1G5M, 1GJH, 1YSW, 2O21, 2O22, 2O2F, 2W3L, 2XA0
Identifikatori
SimboliBCL2; Bcl-2; PPP1R50
Vanjski IDOMIM: 151430 MGI: 88138 HomoloGene: 527 GeneCards: BCL2 Gene
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez59612043
EnsemblENSG00000171791ENSMUSG00000057329
UniProtP10415Q4VBF6
RefSeq (mRNA)NM_000633.2NM_009741.3
RefSeq (protein)NP_000624.2NP_033871.2
Lokacija (UCSC)Chr 18:
60.79 - 60.99 Mb		Chr 1:
108.43 - 108.61 Mb
PubMed pretraga[1][2]

Bcl-2 (B-ćelijski limfom 2) je član Bcl-2 familije proteinskih regulatora apoptoze. On je kodiran BCL2 genom.[1][2] Bcl-2 je drugi član niza proteina koji su inicijalno bili opisani u kontekstu hromozomske translokacije hromozoma 14 i 18 kod folikularnih limfoma. Bcl-2 ortolozi[3] postoje kod mnogobrojnih sisara. Dve izoforme Bcl-2, Izoforma 1, takođe poznata kao 1G5M, i Izoforma 2, poznata kao 1G5O/1GJH, imaju sličnu prostornu strukturu. Međutim, one se razlikuju u njihovoj sposobnosti vezivanja BAD u BAK proteina, kao i po strukturnoj topologiji i elektrostatičkom potencijalu vezujućeg žljeba. Iz toga sledi da Bcl-2 izoforme imaju različite antiapoptotičke aktivnosti.[4]

Interakcije

Bcl-2 formira interakcije sa RAD9A,[5] BAK1,[6][7] Retikulon 4,[8] Bcl-2 asocirani X protein,[5][6][9][10] Kaspaza 8,[11][12] BECN1,[13] SOD1,[14] Bcl-2 interagujući ubica,[15][16] BH3 interagujući domen agonista umiranja,[15][17] RRAS,[18] C-Raf,[19] BCL2L11,[15][20][21] BNIPL,[22][23] HRK,[15][24] PSEN1,[25] BMF,[26] BNIP2,[22][27] BNIP3,[27][28] Faktor rasta nerva IB,[6] BCL2-sličan 1,[6][29] Myc,[30] BCAP31,[31] SMN1,[32] CAPN2,[33] PPP2CA,[34] Noxa,[15][35] Cdk1,[36][37] TP53BP2,[38] Bcl-2 vezan promoter smrti[15][39] i IRS1.[40]

Ljudski BCL-2 geni

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

Reference

  1. ↑ Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM (November 1984). „Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation”. Science 226 (4678): 1097–99. DOI:10.1126/science.6093263. PMID 6093263. 
  2. ↑ Cleary ML, Smith SD, Sklar J (October 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”. Arhivirano iz originala na datum 2015-09-24. Pristupljeno 2014-03-18. 
  4. ↑ „Human Bcl2, Isoform 1”. 
  5. ↑ 5,0 5,1 Komatsu, K; Miyashita T, Hang H, Hopkins K M, Zheng W, Cuddeback S, Yamada M, Lieberman H B, Wang H G (January 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 10620799. 
  6. ↑ 6,0 6,1 6,2 6,3 Lin, Bingzhen; Kolluri Siva Kumar, Lin Feng, Liu Wen, Han Young-Hoon, Cao Xihua, Dawson Marcia I, Reed John C, Zhang Xiao-kun (February 2004). „Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3”. Cell (United States) 116 (4): 527–40. DOI:10.1016/S0092-8674(04)00162-X. ISSN 0092-8674. PMID 14980220. 
  7. ↑ 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 (December 2001). „Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening”. J. Med. Chem. (United States) 44 (25): 4313–24. DOI:10.1021/jm010016f. ISSN 0022-2623. PMID 11728179. 
  8. ↑ Tagami, S; Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (November 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. 
  9. ↑ Hoetelmans, R W M (June 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. 
  10. ↑ Oltvai, Z N; Milliman C L, Korsmeyer S J (August 1993). „Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death”. Cell (UNITED STATES) 74 (4): 609–19. DOI:10.1016/0092-8674(93)90509-O. ISSN 0092-8674. PMID 8358790. 
  11. ↑ Poulaki, V; Mitsiades N, Romero M E, Tsokos M (June 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. 
  12. ↑ Guo, Yin; Srinivasula Srinivasa M, Druilhe Anne, Fernandes-Alnemri Teresa, Alnemri Emad S (April 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. 
  13. ↑ Liang, X H; Kleeman L K, Jiang H H, Gordon G, Goldman J E, Berry G, Herman B, Levine B (November 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. PMC 110269. PMID 9765397. 
  14. ↑ Pasinelli, Piera; Belford Mary Elizabeth, Lennon Niall, Bacskai Brian J, Hyman Bradley T, Trotti Davide, Brown Robert H (July 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. 
  15. ↑ 15,0 15,1 15,2 15,3 15,4 15,5 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 (February 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. 
  16. ↑ Gillissen, Bernhard; Essmann Frank, Graupner Vilma, Stärck Lilian, Radetzki Silke, Dörken Bernd, Schulze-Osthoff Klaus, Daniel Peter T (July 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. PMC 165613. PMID 12853473. 
  17. ↑ Real, Pedro Jose; Cao Yeyu, Wang Renxiao, Nikolovska-Coleska Zaneta, Sanz-Ortiz Jaime, Wang Shaomeng, Fernandez-Luna Jose Luis (November 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. 
  18. ↑ Fernandez-Sarabia, M J; Bischoff J R (November 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. 
  19. ↑ Wang, H G; Rapp U R, Reed J C (November 1996). „Bcl-2 targets the protein kinase Raf-1 to mitochondria”. Cell (UNITED STATES) 87 (4): 629–38. DOI:10.1016/S0092-8674(00)81383-5. ISSN 0092-8674. PMID 8929532. 
  20. ↑ O'Connor, L; Strasser A, O'Reilly L A, Hausmann G, Adams J M, Cory S, Huang D C (January 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. PMC 1170389. PMID 9430630. 
  21. ↑ Hsu, S Y; Lin P, Hsueh A J (September 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. DOI:10.1210/me.12.9.1432. ISSN 0888-8809. PMID 9731710. 
  22. ↑ 22,0 22,1 Qin, Wenxin; Hu Jian, Guo Minglei, Xu Jian, Li Jinjun, Yao Genfu, Zhou Xiaomei, Jiang Huiqiu, Zhang Pingping, Shen Li, Wan Dafang, Gu Jianren (August 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. DOI:10.1016/S0006-291X(03)01387-1. ISSN 0006-291X. PMID 12901880. 
  23. ↑ Yasuda, M; Han J W, Dionne C A, Boyd J M, Chinnadurai G (February 1999). „BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3”. Cancer Res. (UNITED STATES) 59 (3): 533–7. ISSN 0008-5472. PMID 9973195. 
  24. ↑ Inohara, N; Ding L, Chen S, Núñez G (April 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. PMC 1169772. PMID 9130713. 
  25. ↑ 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 (October 1999). „Presenilin 1 protein directly interacts with Bcl-2”. J. Biol. Chem. (UNITED STATES) 274 (43): 30764–9. DOI:10.1074/jbc.274.43.30764. ISSN 0021-9258. PMID 10521466. 
  26. ↑ Puthalakath, H; Villunger A, O'Reilly L A, Beaumont J G, Coultas L, Cheney R E, Huang D C, Strasser A (September 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 11546872. 
  27. ↑ 27,0 27,1 Boyd, J M; Malstrom S, Subramanian T, Venkatesh L K, Schaeper U, Elangovan B, D'Sa-Eipper C, Chinnadurai G (October 1994). „Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins”. Cell (UNITED STATES) 79 (2): 341–51. DOI:10.1016/0092-8674(94)90202-X. ISSN 0092-8674. PMID 7954800. 
  28. ↑ Ray, R; Chen G, Vande Velde C, Cizeau J, Park J H, Reed J C, Gietz R D, Greenberg A H (January 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. DOI:10.1074/jbc.275.2.1439. ISSN 0021-9258. PMID 10625696. 
  29. ↑ Zhang, Haichao; Nimmer Paul, Rosenberg Saul H, Ng Shi-Chung, Joseph Mary (August 2002). „Development of a high-throughput fluorescence polarization assay for Bcl-x(L)”. Anal. Biochem. (United States) 307 (1): 70–5. DOI:10.1016/S0003-2697(02)00028-3. ISSN 0003-2697. PMID 12137781. 
  30. ↑ Jin, Zhaohui; Gao Fengqin, Flagg Tammy, Deng Xingming (September 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. 
  31. ↑ Ng, F W; Nguyen M, Kwan T, Branton P E, Nicholson D W, Cromlish J A, Shore G C (October 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. DOI:10.1083/jcb.139.2.327. ISSN 0021-9525. PMC 2139787. PMID 9334338. 
  32. ↑ Iwahashi, H; Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (November 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. 
  33. ↑ 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 (July 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. 
  34. ↑ Deng, X; Ito T, Carr B, Mumby M, May W S (December 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. DOI:10.1074/jbc.273.51.34157. ISSN 0021-9258. PMID 9852076. 
  35. ↑ 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. DOI:10.1126/science.288.5468.1053. ISSN 0036-8075. PMID 10807576. 
  36. ↑ Pathan, N; Aime-Sempe C, Kitada S, Basu A, Haldar S, Reed J C (2001). „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. PMC 1506558. PMID 11774038. 
  37. ↑ Pathan, N; Aime-Sempe C, Kitada S, Haldar S, Reed J C (2001). „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. PMC 1505024. PMID 11326318. 
  38. ↑ Naumovski, L; Cleary M L (July 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. PMC 231385. PMID 8668206. 
  39. ↑ Yang, E; Zha J, Jockel J, Boise L H, Thompson C B, Korsmeyer S J (January 1995). „Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death”. Cell (UNITED STATES) 80 (2): 285–91. DOI:10.1016/0092-8674(95)90411-5. ISSN 0092-8674. PMID 7834748. 
  40. ↑ 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 (February 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. PMC 14806. PMID 10679027. 

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