c-Jun promotes cellular survival by suppression of PTEN

K. Hettinger, F. Vikhanskaya, M. K. Poh, M. K. Lee, I. de Belle, J. T. Zhang, S. A.G. Reddy, K. Sabapathy

Research output: Contribution to journalArticle

102 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)218-229
Number of pages12
JournalCell Death and Differentiation
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2007

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Hettinger, K., Vikhanskaya, F., Poh, M. K., Lee, M. K., de Belle, I., Zhang, J. T., Reddy, S. A. G., & Sabapathy, K. (2007). c-Jun promotes cellular survival by suppression of PTEN. Cell Death and Differentiation, 14(2), 218-229. https://doi.org/10.1038/sj.cdd.4401946