PIASx is a transcriptional co-repressor of signal transducer and activator of transcription 4

Taruna Arora, Bin Liu, Hongchin He, Jenny Kim, Theresa L. Murphy, Kenneth M. Murphy, Robert L. Modlin, Ke Shuai

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

In response to interleukin 12 (IL-12) stimulation, a latent cytoplasmic transcription factor, Stat4 (signal transducer and activator of transcription 4), becomes tyrosine-phosphorylated and translocates into the nucleus where it binds to DNA to activate transcription. Cofactors that can directly bind and regulate Stat4 activity have not been described. We report here that PIASx, a member of the protein inhibitor of activated STAT (PIAS) family, is a negative regulator of Stat4. PIASx becomes associated with Stat4 following IL-12 stimulation in vivo. PIASx inhibits IL-12-stimulated and Stat4-dependent gene activation in human T cells. PIASx does not inhibit the DNA binding activity of Stat4. Instead PIASx is present in the Stat4-DNA binding complex. Finally the inhibitory activity of PIASx on Stat4-mediated gene activation is abolished by the histone deacetylase inhibitor trichostatin A. Our results suggest that PIASx may function as a co-repressor of Stat4.

Original languageEnglish
Pages (from-to)21327-21330
Number of pages4
JournalJournal of Biological Chemistry
Volume278
Issue number24
DOIs
StatePublished - Jun 13 2003

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