Collaborator of Stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates Stat6-dependent gene transcription.

Goenka S, Cho SH, Boothby M
J Biol Chem. 2007 282 (26): 18732-9

PMID: 17478423 · DOI:10.1074/jbc.M611283200

The transcription factor Stat6 plays a critical role in interleukin-4-dependent gene activation. To mediate this function, Stat6 recruits canonical transcriptional co-activators including the histone acetyl transferases CREB-binding protein and NCoA-1 and other proteins such as a p100 co-factor. However, much remains unknown regarding the constituents of Stat6 enhancer complexes, and the exact molecular events that modulate Stat6-dependent gene activation are not fully understood. Recently, we identified a novel co-factor, CoaSt6 (collaborator of Stat6), which associates with Stat6 and enhances its transcriptional activity. Sequence homologies place CoaSt6 in a superfamily of poly(ADP-ribosyl)polymerase (PARP)-like proteins. We have demonstrated here that PARP enzymatic activity is associated with CoaSt6, and this function of CoaSt6 can append ADP-ribose to itself and p100. Further, we show that a catalytically inactive mutant of CoaSt6 was unable to enhance Stat6-mediated transcription of a test promoter. Consistent with these findings, chemical inhibition of PARP activity blocked interleukin-4-dependent transcription from target promoters in vivo. Taken together, we have identified a CoaSt6-associated PARP activity and provided evidence for a role of poly(ADP ribosyl)ation in Stat-mediated transcriptional responses involving a novel PARP.

MeSH Terms (23)

Amino Acid Sequence Animals Carcinoma, Hepatocellular Catalysis Cell Line, Tumor Enzyme Activation Genes, Reporter Humans Interleukin-4 Kidney Liver Neoplasms Lymphoma, B-Cell Mice Molecular Sequence Data NAD Poly(ADP-ribose) Polymerases Poly Adenosine Diphosphate Ribose STAT6 Transcription Factor Substrate Specificity Trans-Activators Transcription, Genetic Transcriptional Activation Transfection

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