| First Author | Olabisi OA | Year | 2008 |
| Journal | Mol Cell Biol | Volume | 28 |
| Issue | 9 | Pages | 2860-71 |
| PubMed ID | 18299389 | Mgi Jnum | J:135691 |
| Mgi Id | MGI:3794270 | Doi | 10.1128/MCB.01746-07 |
| Citation | Olabisi OA, et al. (2008) Regulation of transcription factor NFAT by ADP-ribosylation. Mol Cell Biol 28(9):2860-71 |
| abstractText | 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. |
