c-Jun promotes cellular survival by suppression of PTEN.
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.
Hettinger
K
K
Laboratory of Molecular Carcinogenesis, Division of Cellular and Molecular Research, National Cancer Centre, 11, Hospital Drive, Singapore 169610, Singapore.
Vikhanskaya
F
F
Poh
M K
MK
Lee
M K
MK
de Belle
I
I
Zhang
J-T
JT
Reddy
S A G
SA
Sabapathy
K
K