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Sumoylation of the Transcription Factor NFATc1 Leads to Its Subnuclear Relocalization and Interleukin-2 Repression by Histone Deacetylase*S⃞

By Arnab Nayak, Judith Glöckner-Pagel, Martin Vaeth, Julia E. Schumann, Mathias Buttmann, Tobias Bopp, Edgar Schmitt, Edgar Serfling and Friederike Berberich-Siebelt

Abstract

The family of NFAT (nuclear factor of activated T-cells) transcription factors plays an important role in cytokine gene regulation. In peripheral T-cells NFATc1 and -c2 are predominantly expressed. Because of different promoter and poly(A) site usage as well as alternative splicing events, NFATc1 is synthesized in multiple isoforms. The highly inducible NFATc1/A contains a relatively short C terminus, whereas the longer, constitutively expressed isoform NFATc1/C spans an extra C-terminal peptide of 246 amino acids. Interestingly, this NFATc1/C-specific terminus can be highly sumoylated. Upon sumoylation, NFATc1/C, but not the unsumoylated NFATc1/A, translocates to promyelocytic leukemia nuclear bodies. This leads to interaction with histone deacetylases followed by deacetylation of histones, which in turn induces transcriptionally inactive chromatin. As a consequence, expression of the NFATc1 target gene interleukin-2 is suppressed. These findings demonstrate that the modification by SUMO (small ubiquitin-like modifier) converts NFATc1 from an activator to a site-specific transcriptional repressor, revealing a novel regulatory mechanism for NFATc1 function

Topics: Mechanisms of Signal Transduction
Publisher: American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:2667779
Provided by: PubMed Central
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