Regulation of transcription factor NFAT by ADP-ribosylation

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

Research output: Contribution to journalArticle

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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

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Adenosine Diphosphate
Transcription Factors
Cytokines
T-Lymphocytes
Poly(ADP-ribose) Polymerases
Calcineurin
Post Translational Protein Processing
Interleukin-4
Interleukin-2
Pharmacology
Poly (ADP-Ribose) Polymerase-1
DNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Olabisi, O. A., Soto-Nieves, N., Nieves, E., Yang, T. T. C., Yang, X., Yu, R. Y. L., ... 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

Regulation of transcription factor NFAT by ADP-ribosylation. / Olabisi, Opeyemi A.; Soto-Nieves, Noemi; Nieves, Edward; Yang, Teddy T C; Yang, XiaoYong; Yu, Raymond Y L; Hee, Yun Suk; Macian-Juan, Fernando; Chow, Chi Wing.

In: Molecular and Cellular Biology, Vol. 28, No. 9, 05.2008, p. 2860-2871.

Research output: Contribution to journalArticle

Olabisi, OA, Soto-Nieves, N, Nieves, E, Yang, TTC, Yang, X, Yu, RYL, Hee, YS, Macian-Juan, F & Chow, CW 2008, 'Regulation of transcription factor NFAT by ADP-ribosylation', Molecular and Cellular Biology, vol. 28, no. 9, pp. 2860-2871. https://doi.org/10.1128/MCB.01746-07
Olabisi, Opeyemi A. ; Soto-Nieves, Noemi ; Nieves, Edward ; Yang, Teddy T C ; Yang, XiaoYong ; Yu, Raymond Y L ; Hee, Yun Suk ; Macian-Juan, Fernando ; Chow, Chi Wing. / Regulation of transcription factor NFAT by ADP-ribosylation. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 9. pp. 2860-2871.
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