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Chapter
  • Print publication year: 2011
  • Online publication date: September 2011

5 - The Control of Mitochondrial Apoptosis by the BCL-2 Family

from Part I - General Principles of Cell Death
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Summary

Introduction

A fundamental step in the commitment to apoptosis via the intrinsic pathway is mitochondrial outer membrane permeabilization (MOMP). This step allows the release of proapoptotic proteins from the mitochondrial intermembrane space into the cytoplasm. Once in the cytoplasm, they induce caspase activation, oligonucleosomal DNA cleavage, and other hallmarks of apoptosis. The details of these important events that occur downstream of MOMP are described in Chapter 4. Here we restrict our attention to the molecular mechanisms by which the cell controls this critical event, molecular mechanisms that primarily involve interactions among the family of proteins known as the BCL-2 family.

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Apoptosis
  • Online ISBN: 9780511976094
  • Book DOI: https://doi.org/10.1017/CBO9780511976094
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Bakhshi, A, Jensen, JP, Goldman, P, et al. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985;41:899–906.
Boyd, JM, Gallo, GJ, Elangovan, B, et al. Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins. Oncogene. 1995;11:1921–8.
Cimmino, A, Calin, GA, Fabbri, M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944–9.
Danial, NN, Korsmeyer, SJ. Cell death: critical control points. Cell. 2004;116:205–19.
Deng, J, Carlson, N, Takeyama, K, Dal Cin, P, Shipp, M, Letai, A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007;12:171–85.
Hsu, YT, Youle, RJ. Nonionic detergents induce dimerization among members of the Bcl-2 family. J Biol Chem. 1997;272:13829–34.
Kluck, RM, Bossy-Wetzel, E, Green, DR, Newmeyer, DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997;275:1132–6.
McDonnell, TJ, Korsmeyer, SJ. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991;349:254–6.
Mihara, M, Erster, S, Zaika, A, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11:577–90.
Oltvai, ZN, Milliman, CL, Korsmeyer, SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609–9.
Wei, MC, Zong, WX, Cheng, EH, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001;292:727–30.
Vaux, DL, Cory, S, Adams, JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988;335:440–2.
Vaux, DL, Weissman, IL, Kim, SK. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science. 1992;258:1955–7.
Willis, SN, Fletcher, JI, Kaufmann, T, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science. 2007;315:856–9.
Wolter, KG, Hsu, YT, Smith, CL, Nechushtan, A, Xi, XG, Youle, RJ. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997;139:1281–92.
Zha, J, Harada, H, Yang, E, Jockel, J, Korsmeyer, SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14–3-3 not BCL-X(L). Cell. 1996;87:619–28.
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