Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim
- Author(s)
- Jabbour, AM; Heraud, JE; Daunt, CP; Kaufmann, T; Sandow, J; O'Reilly, LA; Callus, BA; Lopez, A; Strasser, A; Vaux, DL; Ekert, PG;
- Details
- Publication Year 2009-04,Volume 16,Issue #4,Page 555-563
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Publication Type
- Journal Article
- Abstract
- Bcl-2 family members regulate apoptosis in response to cytokine withdrawal and a broad range of cytotoxic stimuli. Pro-apoptotic Bcl-2 family members Bax and Bak are essential for apoptosis triggered by interleukin-3 (IL-3) withdrawal in myeloid cells. The BH3-only protein Puma is critical for initiation of IL-3 withdrawal-induced apoptosis, because IL-3-deprived Puma(-/-) cells show increased capacity to form colonies when IL-3 is restored. To investigate the mechanisms of Puma-induced apoptosis and the interactions between Puma and other Bcl-2 family members, we expressed Puma under an inducible promoter in cells lacking one or more Bcl-2 family members. Puma rapidly induced apoptosis in cells lacking the BH3-only proteins, Bid and Bim. Puma expression resulted in activation of Bax, but Puma killing was not dependent on Bax or Bak alone as Puma readily induced apoptosis in cells lacking either of these proteins, but could not kill cells deficient for both. Puma co-immunoprecipitated with the anti-apoptotic Bcl-2 family members Bcl-xL and Mcl-1 but not with Bax or Bak. These data indicate that Puma functions, in the context of induced overexpression or IL-3 deprivation, primarily by binding and inactivating anti-apoptotic Bcl-2 family members.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- BCL-X-L; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; COLORECTAL-CANCER CELLS; BH3-ONLY PROTEINS PUMA; BH3 DOMAINS; DEATH; SURVIVAL; P53; GENE; RESPONSES
- Publisher's Version
- https://doi.org/10.1038/cdd.2008.179
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2009-04-01 12:00:00