Withdrawal symptoms on display: Bcl-2 members under investigation.
The balance between survival and apoptosis of lymphocytes is considered to be regulated by specific signals delivered through cell surface receptors binding either antigen (fragments) or homeostatic cytokines. Expanding lymphocytes must also compete for nutrients. For growth factors and nutrients, recent data indicate how these generic environmental signals couple to members of the apoptosis-regulating Bcl-2 family. The prosurvival molecule Mcl-1 is engaged by lethal BH3-only proteins Puma and Noxa under these circumstances. We propose that Puma and Noxa have specific roles in tipping the balance towards apoptosis after growth factor withdrawal and nutrient shortage, respectively. These complementary mechanisms tune survival in the various niches when lymphocytes compete for resources during selection and expansion.
Alves
Nuno L
NL
Department of Experimental Immunology, Academic Medical Center, AZ 1105 Amsterdam, The Netherlands.
van Lier
René A W
RA
Eldering
Eric
E
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology*; D013375:Substance Withdrawal Syndrome / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; C498702:PMAIP1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2