Nuclear factor of activated T cells (NFAT) signaling regulates PTEN expression and intestinal cell differentiation

Qingding Wang, Yuning Zhou, Lindsey N. Jackson, Sara M. Johnson, Chi Wing Chow, B. Mark Evers

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The nuclear factor of activated T cell (NFAT) proteins are a family of transcription factors (NFATc1-c4) involved in the regulation of cell differentiation and adaptation. Previously we demonstrated that inhibition of phosphatidylinositol 3-kinase or overexpression of PTEN enhanced intestinal cell differentiation. Here we show that treatment of intestinal-derived cells with the differentiating agent sodium butyrate (NaBT) increased PTEN expression, NFAT binding activity, and NFAT mRNA expression, whereas pretreatment with the NFAT signaling inhibitor cyclosporine A (CsA) blocked NaBT-mediated PTEN induction. Moreover, knockdown of NFATc1 or NFATc4, but not NFATc2 or NFATc3, attenuated NaBT-induced PTEN expression. Knockdown of NFATc1 decreased PTEN expression and increased the phosphorylation levels of Akt and downstream targets Foxo1 and GSK-3α/β. Furthermore, overexpression of NFATc1 or the NFATc4 active mutant increased PTEN and p27kip1 expression and decreased Akt phosphorylation. In addition, pretreatment with CsA blocked NaBT-mediated induction of intestinal alkaline phosphatase (IAP) activity and villin and p27kip1 expression; knockdown of either NFATc1 or NFATc4 attenuated NaBT-induced IAP activity. We provide evidence showing that NFATc1 and NFATc4 are regulators of PTEN expression. Importantly, our results suggest that NFATc1 and NFATc4 regulation of intestinal cell differentiation may be through PTEN regulation.

Original languageEnglish (US)
Pages (from-to)412-420
Number of pages9
JournalMolecular Biology of the Cell
Volume22
Issue number3
DOIs
StatePublished - Feb 1 2011

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NFATC Transcription Factors
Cell Differentiation
Cyclosporine
Alkaline Phosphatase
Phosphorylation
Phosphatidylinositol 3-Kinase
Glycogen Synthase Kinase 3
Butyric Acid
Transcription Factors
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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Nuclear factor of activated T cells (NFAT) signaling regulates PTEN expression and intestinal cell differentiation. / Wang, Qingding; Zhou, Yuning; Jackson, Lindsey N.; Johnson, Sara M.; Chow, Chi Wing; Evers, B. Mark.

In: Molecular Biology of the Cell, Vol. 22, No. 3, 01.02.2011, p. 412-420.

Research output: Contribution to journalArticle

Wang, Qingding ; Zhou, Yuning ; Jackson, Lindsey N. ; Johnson, Sara M. ; Chow, Chi Wing ; Evers, B. Mark. / Nuclear factor of activated T cells (NFAT) signaling regulates PTEN expression and intestinal cell differentiation. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 3. pp. 412-420.
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