Biochemical and Biophysical Research Communications, Vol.353, No.3, 576-581, 2007
Tissue type-specific modulation of ER transcriptional activity by NFAT3
NFAT3 belongs to the NFAT family of transcription factors playing important roles in the development of several organ systems and was found to act as a transcriptional coactivator of estrogen receptors (ER alpha and ER beta) in breast cancer cells. Since some cofactors of transcription factors show cell or tissue type-specific effects on transcriptional regulation, we investigated the effect of NFAT3 on the transcriptional activity of ERs in different cell lines originated from kidney. Surprisingly, overexpression of NFAT3 in these cell types decreased dose-dependently both ER alpha and ER beta transcriptional activities in a ligand-independent manner. Knockdown of endogenous NEAT3 using NFAT3 small interfering RNA (siRNA) increased ER transcriptional activities. NFAT3 deletion mutants lacking the ER-binding sites completely abolished the NFAT3 repression of ER alpha and ER beta transcriptional activities. Replacement of Ser168 and Ser170, the amino acid residues on which NFAT3 can be phosphorylated, with Ala did not change the ability of NFAT3 to inhibit the transcriptional activity of ER alpha and ER beta. Taken together, these results demonstrate that NFAT3 is a new kind of cofactor that displays dual transcription modulation mode dependent on tissue types. (c) 2006 Elsevier Inc. All rights reserved.