Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles
Articolo
Data di Pubblicazione:
2007
Citazione:
Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles / P. Bruno, A. Calastretti, M. Priulla, L. Asnaghi, F. Scarlatti, A. Nicolin, G. Canti. - In: CELLULAR SIGNALLING. - ISSN 0898-6568. - 19:10(2007), pp. 2118-2126. [10.1016/j.cellsig.2007.06.008]
Abstract:
Akt activation assists tumor cell survival and promotes resistance to chemotherapy. Here we show that constitutively active Akt (CA-Akt) cells are highly sensitized to cell death induced by nutrient and growth factor deprivation, whereas dominant-negative Akt (DN-Akt) cells have a high rate of survival. The content of autophagosomes in starved CA-Akt cells was high, while DN-Akt cells expressed autophagic vacuoles constitutively, independently of nutrition conditions. Thus Akt down-regulation and downstream events can induce autophagosomes which were not directly determinants of cell death. Biochemical analysis in Akt-mutated cells show that (i) Akt and mTOR proteins were degraded more rapidly than the housekeeping proteins, (ii) mTOR phosphorylation at position Thr2446 was relatively high in DN-Akt and low in CA-Akt cells, induced by starvation in mock cells only, which suggests reduced autoregulation of these pathways in Akt-mutated cells, (iii) both protein synthesis and protein degradation were significantly higher in starved CA-Akt cells than in starved DN-Akt cells or mock cells. In conclusion, constitutively active Akt, unable to control synthesis and wasting of proteins, accelerates the death of starved cells.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Akt ; Starvation ; Autophagy ; Apoptosis ; mTOR
Elenco autori:
P. Bruno, A. Calastretti, M. Priulla, L. Asnaghi, F. Scarlatti, A. Nicolin, G. Canti
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