Apoptosis in the development and maintenance of the immune system.
Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death domain, designated the Bcl-2 homology 3 (BH3) domain. BH3-only proteins operate as upstream sentinels, selectively sensing both intrinsic and extrinsic death stimuli. They communicate this information to the pro-apoptotic 'multidomain' members Bax or Bak--a process that is antagonized by anti-apoptotic members of the Bcl-2 family. The functional balance of pro-apoptotic versus anti-apoptotic influences, which operates at organelles, determines whether a lymphocyte will live or die. BH3-only molecules, often working in concert, compete for downstream multidomain pro- and anti-apoptotic BCL-2 members to control serial stages of lymphocyte development and homeostasis.
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Joseph T
JT
Opferman
Stanley J
SJ
Korsmeyer
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D020169:Caspases / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D018448:Models, Immunological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology
D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases