Regulation of transcription factor NFAT by ADP-ribosylation

Opeyemi A. Olabisi, Noemi Soto-Nieves, Edward Nieves, Teddy T.C. Yang, Xiao Yong Yang, Raymond Y.L. Yu, Yun Suk Hee, Fernando Macian, Chi Wing Chow

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

ADP-ribosylation is a reversible posttranslational modification mediated by poly-ADP-ribose polymerase (PARP). The results of recent studies demonstrate that ADP-ribosylation contributes to transcription regulation. Here, we report that transcription factor NFAT binds to and is ADP-ribosylated by PARP-1 in an activation-dependent manner. Mechanistically, ADP-ribosylation increases NFAT DNA binding. Functionally, NFAT-mediated interleukin-2 (IL-2) expression was reduced in T cells upon genetic ablation or pharmacological inhibition of PARP-1. Parp-1-/- T cells also exhibit reduced expression of other NFAT-dependent cytokines, such as IL-4. Together, these results demonstrate that ADP-ribosylation mediated by PARP-1 provides a molecular switch to positively regulate NFAT-dependent cytokine gene transcription. These results also imply that, similar to the effect of calcineurin inhibition, PARP-1 inhibition may be beneficial in modulating immune functions.

Original languageEnglish (US)
Pages (from-to)2860-2871
Number of pages12
JournalMolecular and cellular biology
Volume28
Issue number9
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Olabisi, O. A., Soto-Nieves, N., Nieves, E., Yang, T. T. C., Yang, X. Y., Yu, R. Y. L., Hee, Y. S., Macian, F., & Chow, C. W. (2008). Regulation of transcription factor NFAT by ADP-ribosylation. Molecular and cellular biology, 28(9), 2860-2871. https://doi.org/10.1128/MCB.01746-07