Anti-apoptotic BCL-2 Family Members in Development

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2017 Nov 4

PMID 29099482

Citations 116

Authors

Joseph T Opferman

Anisha Kothari

Affiliations

Soon will be listed here.

Abstract

Almost 30 years ago it was first appreciated that anti-apoptotic B-cell lymphoma-2 (BCL-2) prevents the induction of apoptosis not only in malignant cells, but also in normal cellular lineages. This critical observation has rapidly evolved from merely identifying new BCL-2 family members to understanding how their biochemical interactions trigger the cell death process, and, more recently, to pharmacological inhibition of anti-apoptotic BCL-2 function in disease. Indeed, the proper regulation of apoptosis is important in many aspects of life including development, homeostasis, and disease biology. To better understand these processes, scientists have used many tools to assess the contribution of individual anti-apoptotic BCL-2 family members. This review will focus on the prominent roles for BCL-2 and other pro-survival family members in promoting the development of mammals during early embryogenesis, neurogenesis, and hematopoiesis.

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References

Kirito K, Watanabe T, Sawada K, Endo H, Ozawa K, Komatsu N . Thrombopoietin regulates Bcl-xL gene expression through Stat5 and phosphatidylinositol 3-kinase activation pathways. J Biol Chem. 2002; 277(10):8329-37. DOI: 10.1074/jbc.M109824200. View

Clarke P, Posada A, Primi M, Castagne V . Neuronal death in the central nervous system during development. Biomed Pharmacother. 1998; 52(9):356-62. DOI: 10.1016/s0753-3322(99)80002-x. View

Krajewska M, Mai J, Zapata J, Ashwell K, Schendel S, Reed J . Dynamics of expression of apoptosis-regulatory proteins Bid, Bcl-2, Bcl-X, Bax and Bak during development of murine nervous system. Cell Death Differ. 2002; 9(2):145-57. DOI: 10.1038/sj.cdd.4400934. View

Opferman J, Letai A, Beard C, Sorcinelli M, Ong C, Korsmeyer S . Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003; 426(6967):671-6. DOI: 10.1038/nature02067. View

Hardy K . Cell death in the mammalian blastocyst. Mol Hum Reprod. 1997; 3(10):919-25. DOI: 10.1093/molehr/3.10.919. View

Souers A, Leverson J, Boghaert E, Ackler S, Catron N, Chen J . ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013; 19(2):202-8. DOI: 10.1038/nm.3048. View

Muller A, Medvinsky A, Strouboulis J, Grosveld F, Dzierzak E . Development of hematopoietic stem cell activity in the mouse embryo. Immunity. 1994; 1(4):291-301. DOI: 10.1016/1074-7613(94)90081-7. View

Orlofsky A, Weiss L, Kawachi N, Prystowsky M . Deficiency in the anti-apoptotic protein A1-a results in a diminished acute inflammatory response. J Immunol. 2002; 168(4):1840-6. DOI: 10.4049/jimmunol.168.4.1840. View

Haverkamp J, Smith A, Weinlich R, Dillon C, Qualls J, Neale G . Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity. 2014; 41(6):947-59. PMC: 4272664. DOI: 10.1016/j.immuni.2014.10.020. View

10.

Jacobsen S, Borge O, Ramsfjell V, Cui L, Cardier J, Veiby O . Thrombopoietin, a direct stimulator of viability and multilineage growth of primitive bone marrow progenitor cells. Stem Cells. 1996; 14 Suppl 1:173-80. DOI: 10.1002/stem.5530140722. View

11.

Krajewski S, Bodrug S, Krajewska M, Shabaik A, Gascoyne R, Berean K . Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. Am J Pathol. 1995; 146(6):1309-19. PMC: 1870904. View

12.

Miyazaki T, Liu Z, Kawahara A, Minami Y, Yamada K, Tsujimoto Y . Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. Cell. 1995; 81(2):223-31. DOI: 10.1016/0092-8674(95)90332-1. View

13.

Wang X, Bathina M, Lynch J, Koss B, Calabrese C, Frase S . Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes Dev. 2013; 27(12):1351-64. PMC: 3701191. DOI: 10.1101/gad.215855.113. View

14.

LINDSTEN T, Ross A, King A, Zong W, Rathmell J, Shiels H . The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell. 2001; 6(6):1389-99. PMC: 3057227. DOI: 10.1016/s1097-2765(00)00136-2. View

15.

Ross A, Waymire K, Moss J, Parlow A, Skinner M, Russell L . Testicular degeneration in Bclw-deficient mice. Nat Genet. 1998; 18(3):251-6. DOI: 10.1038/ng0398-251. View

16.

Sathe P, Delconte R, Souza-Fonseca-Guimaraes F, Seillet C, Chopin M, Vandenberg C . Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nat Commun. 2014; 5:4539. DOI: 10.1038/ncomms5539. View

17.

Thomas R, Roberts D, Kubli D, Lee Y, Quinsay M, Owens J . Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure. Genes Dev. 2013; 27(12):1365-77. PMC: 3701192. DOI: 10.1101/gad.215871.113. View

18.

Magiera M, Mora S, Mojsa B, Robbins I, Lassot I, Desagher S . Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons. Cell Death Differ. 2012; 20(2):281-92. PMC: 3554334. DOI: 10.1038/cdd.2012.124. View

19.

Debrincat M, Josefsson E, James C, Henley K, Ellis S, Lebois M . Mcl-1 and Bcl-x(L) coordinately regulate megakaryocyte survival. Blood. 2012; 119(24):5850-8. DOI: 10.1182/blood-2011-12-398834. View

20.

Garcia I, Martinou I, Tsujimoto Y, Martinou J . Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science. 1992; 258(5080):302-4. DOI: 10.1126/science.1411528. View