Regulation of transcription factor NFAT by ADP-ribosylation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Olabisi, OA; Soto-Nieves, N; Nieves, E; Yang, TTC; Yang, X; Yu, RYL; Suk, HY; Macian, F; Chow, C-W

Published Date

  • May 2008

Published In

Volume / Issue

  • 28 / 9

Start / End Page

  • 2860 - 2871

PubMed ID

  • 18299389

Pubmed Central ID

  • 18299389

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.01746-07

Language

  • eng

Conference Location

  • United States