Regulation of Transcription Factor NFAT by ADP-Ribosylation
Year: 2008
Type: article
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.
Source: Molecular and Cellular Biology
DOI: 10.1128/mcb.01746-07
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: American Diabetes Association, American Heart Association, National Institutes of Health, Albert Einstein College of Medicine, Yeshiva University, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
OpenAlex ID: W2109690762