Apoptosis induced by overall metabolic stress converges on the Bcl-2 family proteins Noxa and Mcl-1.
Apoptosis
; 16(7): 708-21, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21516346
ABSTRACT
Apoptosis provoked by glucose shortage in dividing T cells is mediated via the BH3-only protein Noxa and inhibition of its binding partner Mcl-1. It is unknown how signals from cellular metabolism can affect the balance between Mcl-1 and Noxa and to what extent other Bcl-2 members are involved in this apoptosis cascade. Here, we defined the mechanism underlying apoptosis in relation to various types of metabolic stress. First, we established that the Noxa/Mcl-1 balance is regulated by glucose deprivation as well as by general metabolic stress, via changes in proteasome-mediated degradation of Mcl-1. Second, in contrast with cytokine-deprivation, no transcriptional modulation of Mcl-1, Puma, Bim or Noxa was observed during glucose deprivation. Third, no changes in PKB or GSK3 activity occurred and no clear role for AMPK was detected. Fourth, apoptosis triggered by nutrient deprivation was executed without signs of overt autophagy and independent of ROS production or p38 MAP kinase activity. Lastly, apoptosis under nutrient limitation could also be delayed by knock-down of Bim or overexpression of Bcl-2. In conclusion, Noxa functions in a specific apoptotic pathway that integrates overall nutrient stress, independent from attenuated PI3K/PKB signaling and without clear involvement of autophagy.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estrés Fisiológico
/
Apoptosis
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Proteínas Proto-Oncogénicas c-bcl-2
Límite:
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article