Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction
- Author(s)
- Erlacher, M; Labi, V; Manzl, C; Bock, G; Tzankov, A; Hacker, G; Michalak, E; Strasser, A; Villunger, A;
- Details
- Publication Year 2006-12-25,Volume 203,Issue #13,Page 2939-2951
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- The physiological role of B cell lymphoma 2 (Bcl-2) homology 3-only proteins has been investigated in mice lacking the individual genes identifying rate-limiting roles for Bim (Bcl-2-interacting mediator of cell death) and Puma (p53-up-regulated modulator of apoptosis) in apoptosis induction. The loss of Bim protects lymphocytes from apoptosis induced by cytokine deprivation and deregulated Ca++ flux and interferes with the deletion of autoreactive lymphocytes and the shutdown of immune responses. In contrast, Puma is considered the key mediator of p53-induced apoptosis. To investigate the hypothesis that Bim and Puma have overlapping functions, we generated mice lacking both genes and found that bim(-/-)/puma(-/-) animals develop multiple postnatal defects that are not observed in the single knockout mice. Most strikingly, hyperplasia of lymphatic organs is comparable with that observed in mice overexpressing Bcl-2 in all hemopoietic cells exceeding the hyperplasia observed in bim(-/-) mice. Bim and Puma also have clearly overlapping functions in p53-dependent and -independent apoptosis. Their combined loss promotes spontaneous tumorigenesis, causing the malignancies observed in Bcl-2 transgenic mice, but does not exacerbate the autoimmunity observed in the absence of Bim.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- FAMILY-MEMBER BIM; TRANSGENIC MICE; IN-VIVO; BCL-2; SURVIVAL; PATHWAYS; BAX; P53; HOMEOSTASIS; DEFICIENCY
- Publisher's Version
- https://doi.org/10.1084/jem.20061552
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- Refer to copyright notice on published article.
Creation Date: 2006-12-25 12:00:00