c-Jun promotes cellular survival by suppression of PTEN

K. Hettinger, F. Vikhanskaya, M. K. Poh, M. K. Lee, I. de Belle, Jian-Ting Zhang, S. A G Reddy, K. Sabapathy

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

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Transcription Factor AP-1
Survival
Tumor Cell Line
Small Interfering RNA
Cell Survival
Cell Death
Fibroblasts
Apoptosis
Cell Line
Food
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hettinger, K., Vikhanskaya, F., Poh, M. K., Lee, M. K., de Belle, I., Zhang, J-T., ... 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

c-Jun promotes cellular survival by suppression of PTEN. / Hettinger, K.; Vikhanskaya, F.; Poh, M. K.; Lee, M. K.; de Belle, I.; Zhang, Jian-Ting; Reddy, S. A G; Sabapathy, K.

In: Cell Death and Differentiation, Vol. 14, No. 2, 02.2007, p. 218-229.

Research output: Contribution to journalArticle

Hettinger, K, Vikhanskaya, F, Poh, MK, Lee, MK, de Belle, I, Zhang, J-T, Reddy, SAG & Sabapathy, K 2007, 'c-Jun promotes cellular survival by suppression of PTEN', Cell Death and Differentiation, vol. 14, no. 2, pp. 218-229. https://doi.org/10.1038/sj.cdd.4401946
Hettinger K, Vikhanskaya F, Poh MK, Lee MK, de Belle I, Zhang J-T et al. c-Jun promotes cellular survival by suppression of PTEN. Cell Death and Differentiation. 2007 Feb;14(2):218-229. https://doi.org/10.1038/sj.cdd.4401946
Hettinger, K. ; Vikhanskaya, F. ; Poh, M. K. ; Lee, M. K. ; de Belle, I. ; Zhang, Jian-Ting ; Reddy, S. A G ; Sabapathy, K. / c-Jun promotes cellular survival by suppression of PTEN. In: Cell Death and Differentiation. 2007 ; Vol. 14, No. 2. pp. 218-229.
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