c-Jun promotes cellular survival by suppression of PTEN
Hettinger, K. Vikhanskaya, F. Poh, M.K. Lee, M.K. de Belle, I. Zhang, J.-T. Reddy, S.A.G. Sabapathy, K.
Hettinger, K.
Vikhanskaya, F.
Poh, M.K.
Lee, M.K.
de Belle, I.
Zhang, J.-T.
Reddy, S.A.G.
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Alternative Title
Abstract
Activation of c-Jun, a component of the AP-1 family of transcription factors, leads to either promotion or prevention of apoptosis. However, the molecular determinants of c-Jun-mediated cell survival are still unclear. We show here that inducible expression of c-Jun promotes cellular survival by negatively regulating the expression of the tumor-suppressor PTEN, resulting in the concomitant activation of the Akt survival pathway. Consistently, c-jun-/- fibroblasts, which are sensitive to nutrient deprivation, and human cell lines in which c-Jun expression is silenced, express elevated levels of PTEN. siRNA-mediated silencing of PTEN resulted in the reduction of cell-death owing to c-Jun deficiency. c-Jun was found to suppress PTEN expression by binding to a variant AP-1 site found in the 5′ upstream sequences of PTEN promoter. Finally, an inverse correlation between c-Jun and PTEN levels was apparent in a panel of human tumor cell lines, independent of their p53 status. Together, the data demonstrate that c-Jun contributes to the promotion of cellular survival by regulating the expression of PTEN.
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Source Title
Cell Death and Differentiation
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Date
2007-02
DOI
10.1038/sj.cdd.4401946
Type
Article