Puma indirectly activates Bax to cause apoptosis in the absence of Bid or Bim.
Cell Death Differ
; 16(4): 555-63, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19079139
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-x(L) 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas
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Apoptosis
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Proteínas Supresoras de Tumor
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Proteínas Reguladoras de la Apoptosis
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Proteína X Asociada a bcl-2
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Proteína Proapoptótica que Interacciona Mediante Dominios BH3
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2009
Tipo del documento:
Article
País de afiliación:
Australia