title: Collaborator of Stat6 (CoaSt6)-associated poly(ADP-ribose) polymerase activity modulates Stat6-dependent gene transcription.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2363, USA. shreevrat.goenka@vanderbilt.edu
authors.forename: Shreevrat
authors.initials: S
authors.lastname: Goenka
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Cho
authors.forename: Mark
authors.initials: M
authors.lastname: Boothby
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002384:Catalysis; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D017930:Genes, Reporter; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008113:Liver Neoplasms; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000235:genetics* / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D013379:Substrate Specificity; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection
chemical_list: D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D009243:NAD; D015847:Interleukin-4; D011064:Poly Adenosine Diphosphate Ribose; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases