An interconnected hierarchical model of cell death regulation by the BCL-2 family

Nature Cell Biology

Volumn 17, Issue 10, 2015, Pages 1270-1281

  Chen, Hui Chen ^a   Kanai, Masayuki ^a   Inoue Yamauchi, Akane ^a   Tu, Ho Chou ^a   Huang, Yafen ^a   Ren, Decheng ^b   Kim, Hyungjin ^c   Takeda, Shugaku ^a   Reyna, Denis E ^d   Chan, Po M ^a   Ganesan, Yogesh Tengarai ^a   Liao, Chung Ping ^a   Gavathiotis, Evripidis ^d   Hsieh, James J ^a   Cheng, Emily H ^a,e  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c STONY BROOK UNIVERSITY   (United States)

^d ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^e WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BH3 PROTEIN; BIM PROTEIN; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN BID; PROTEIN MCL 1; PROTEIN NOXA; PUMA PROTEIN; APOPTOSIS REGULATORY PROTEIN; BCL2L11 PROTEIN, HUMAN; BCL2L11 PROTEIN, MOUSE; CYTOCHROME C; MEMBRANE PROTEIN; ONCOPROTEIN; PMAIP1 PROTEIN, MOUSE; PUMA PROTEIN, MOUSE; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BAK GENE; BAX GENE; BID GENE; BIM GENE; BIOCHEMICAL ANALYSIS; BIOLOGICAL MODEL; CELL DEATH; CELL SURVIVAL; CONTROLLED STUDY; DOWN REGULATION; EMBRYO; FEMALE; MALE; MOLECULAR GENETICS; MOUSE; NONHUMAN; NOXA GENE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; PUMA GENE; REGULATORY MECHANISM; ANIMAL; APOPTOSIS; C57BL MOUSE; CELL CULTURE; CYTOLOGY; FIBROBLAST; GENETICS; IMMUNOBLOTTING; KNOCKOUT MOUSE; MAMMALIAN EMBRYO; METABOLISM; MITOCHONDRION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SMALL INTESTINE;

ANIMALS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; BCL-2 HOMOLOGOUS ANTAGONIST-KILLER PROTEIN; BCL-2-ASSOCIATED X PROTEIN; BCL-2-LIKE PROTEIN 11; BH3 INTERACTING DOMAIN DEATH AGONIST PROTEIN; CELLS, CULTURED; CYTOCHROMES C; EMBRYO, MAMMALIAN; FIBROBLASTS; IMMUNOBLOTTING; INTESTINE, SMALL; MEMBRANE PROTEINS; MICE, INBRED C57BL; MICE, KNOCKOUT; MITOCHONDRIA; MODELS, BIOLOGICAL; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-BCL-2; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TUMOR SUPPRESSOR PROTEINS;

EID: 84942991698     PISSN: 14657392     EISSN: 14764679     Source Type: Journal    
DOI: 10.1038/ncb3236     Document Type: Article

References (53)

1. Gross, A., McDonnell, J. M. & Korsmeyer, S. J. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911 (1999).
2. Youle, R. J. & Strasser, A. The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9, 47-59 (2008).
3. Czabotar, P. E., Lessene, G., Strasser, A. & Adams, J. M. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat. Rev. Mol. Cell Biol. 15, 49-63 (2014).
4. Wang, X. The expanding role of mitochondria in apoptosis. Genes Dev. 15, 2922-2933 (2001).
5. Newmeyer, D. D. & Ferguson-Miller, S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112, 481-490 (2003).
6. Kim, H. et al. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat. Cell Biol. 8, 1348-1358 (2006).
7. Westphal, D., Kluck, R. M. & Dewson, G. Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ. 21, 196-205 (2014).
8. Wei, M C. et Al. TBID, A Membrane-Targeted Death Ligand, Oligomerizes BAK to Release Cytochrome C. Genes Dev. 14, 2060-2071 (2000).
9. Cheng, E. H. et al. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX-And BAK-mediated mitochondrial apoptosis. Mol. Cell 8, 705-711 (2001).
10. Letai, A. et al. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2, 183-192 (2002).
11. Chen, L. et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17, 393-403 (2005).
12. Kuwana, T. et al. BH3 domains of BH3-only proteins differentially regulate Baxmediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell 17, 525-535 (2005).
13. Certo, M. et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9, 351-365 (2006).
14. Kim, H. et al. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol. Cell 36, 487-499 (2009).
15. Ren, D. et al. BID, BIM, and PUMA are essential for activation of the BAX-And BAK-dependent cell death program. Science 330, 1390-1393 (2010).
16. Sattler, M. et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275, 983-986 (1997).
17. Czabotar, P. E. et al. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc. Natl Acad. Sci. USA 104, 6217-6222 (2007).
18. Czabotar, P. E. et al. Bax crystal structures reveal how BH3 domains activate Bax and nucleate its oligomerization to induce apoptosis. Cell 152, 519-531 (2013).
19. Moldoveanu, T. et al. BID-induced structural changes in BAK promote apoptosis. Nat. Struct. Mol. Biol. 20, 589-597 (2013).
20. Leshchiner, E. S., Braun, C. R., Bird, G. H. & Walensky, L. D. Direct activation of full-length proapoptotic BAK. Proc. Natl Acad. Sci. USA 110, E986-E995 (2013).
21. Edwards, A. L. et al. Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3. Chem. Biol. 20, 888-902 (2013).
22. Brouwer, J. M. et al. Bak core and latch domains separate during activation, and freed core domains form symmetric homodimers. Mol. Cell 55, 938-946 (2014).
23. Dewson, G. et al. To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3: groove interactions. Mol. Cell 30, 369-380 (2008).
24. Gavathiotis, E., Reyna, D. E., Davis, M. L., Bird, G. H. & Walensky, L. D. BH3-Triggered structural reorganization drives the activation of proapoptotic BAX. Mol. Cell 40, 481-492 (2010).
25. Wei, M. C. et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292, 727-730 (2001).
26. Desagher, S. et al. Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J. Cell Biol. 144, 891-901 (1999).
27. Willis, S. N. et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315, 856-859 (2007).
28. Lindsten, T. et al. The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues. Mol. Cell 6, 1389-1399 (2000).
29. Martinou, J. C. & Youle, R. J. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev. Cell 21, 92-101 (2011).
30. Scorrano, L. et al. BAX and BAK regulation of endoplasmic reticulum Ca2C: a control point for apoptosis. Science 300, 135-139 (2003).
31. Kuwana, T. et al. Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111, 331-342 (2002).
32. Lovell, J. F. et al. Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell 135, 1074-1084 (2008).
33. Villunger, A. et al. p53-And drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302, 1036-1038 (2003).
34. Shibue, T. et al. Integral role of Noxa in p53-mediated apoptotic response. Genes Dev. 17, 2233-2238 (2003).
35. Naik, E., Michalak, E. M., Villunger, A., Adams, J. M. & Strasser, A. Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa. J. Cell Biol. 176, 415-424 (2007).
36. Lowe, S. W., Ruley, H. E., Jacks, T. & Housman, D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957-967 (1993).
37. Cheng, E. H., Sheiko, T. V., Fisher, J. K., Craigen, W. J. & Korsmeyer, S. J. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301, 513-517 (2003).
38. Willis, S. N. et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 19, 1294-1305 (2005).
39. Tu, H. C. et al. The p53-cathepsin axis cooperates with ROS to activate programmed necrotic death upon DNA damage. Proc. Natl Acad. Sci. USA 106, 1093-1098 (2009).
40. Cheng, E. H., Levine, B., Boise, L. H., Thompson, C. B. & Hardwick, J. M. Baxindependent inhibition of apoptosis by Bcl-XL. Nature 379, 554-556 (1996).
41. Gavathiotis, E. et al. BAX activation is initiated at a novel interaction site. Nature 455, 1076-1081 (2008).
42. Westphal, D., Dewson, G., Czabotar, P. E. & Kluck, R. M. Molecular biology of Bax and Bak activation and action. Biochim. Biophys. Acta 1813, 521-531 (2011).
43. Edlich, F. et al. Bcl-xL retrotranslocates Bax from the mitochondria into the cytosol. Cell 145, 104-116 (2011).
44. Walensky, L. D. et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305, 1466-1470 (2004).
45. Fu, N. Y., Sukumaran, S. K., Kerk, S. Y. & Yu, V. C. Baxbeta: a constitutively active human Bax isoform that is under tight regulatory control by the proteasomal degradation mechanism. Mol. Cell 33, 15-29 (2009).
46. Du, H. et al. BH3 domains other than Bim and Bid can directly activate Bax/Bak. J. Biol. Chem. 286, 491-501 (2011).
47. Dai, H. et al. Transient binding of an activator BH3 domain to the Bak BH3-binding groove initiates Bak oligomerization. J. Cell Biol. 194, 39-48 (2011).
48. Oltersdorf, T. et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435, 677-681 (2005).
49. Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421-3428 (2008).
50. Souers, A. J. et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med. 19, 202-208 (2013).
51. Davids, M. S. & Letai, A. Targeting the B-cell lymphoma/leukemia 2 family in cancer. J. Clin. Oncol. 30, 3127-3135 (2012).
52. Walensky, L. D. From mitochondrial biology to magic bullet: navitoclax disarms BCL-2 in chronic lymphocytic leukemia. J. Clin. Oncol. 30, 554-557 (2012).
53. Anderson, M. A., Huang, D. & Roberts, A. Targeting BCL2 for the treatment of lymphoid malignancies. Semin. Hematol. 51, 219-227 (2014).