title: Identification of STAT3-independent regulatory effects for protein inhibitor of activated STAT3 by binding to novel transcription factors.
abstract: Protein Inhibitor of Activated Signal Transducer and Activators of Transcription 3 (PIAS3) is a molecule that regulates STAT3 and has antiproliferative properties. Glioblastoma and squamous cell lung cancer lack PIAS3 expression. To test the hypothesis that PIAS3 transcriptional effects are STAT3-independent, we developed models for STAT3 knockdown and PIAS3 over-expression. PIAS3 expression results in a distinct transcriptional profile that does not occur with STAT3 knockdown. We identify novel transcription factor binding partners for PIAS3 including ETS, EGR1, NR1I2, and GATA1. PIAS3 binds to these factors and regulates their transcriptional effects resulting in alterations in canonical pathways including Wnt/β-catenin signaling and functions such as cell death and proliferation. A model is proposed by which PIAS3 effects EGR1 regulated pathways.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH USA.
authors.forename: Snehal
authors.initials: S
authors.lastname: Dabir
authors.forename: Amy
authors.initials: A
authors.lastname: Kluge
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Aziz
authors.forename: Janet A
authors.initials: JA
authors.lastname: Houghton
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053858:Metabolic Networks and Pathways; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D000077297:Pregnane X Receptor; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D018832:Molecular Chaperones; C000625852:NR1I2 protein, human; C484745:PIAS3 protein, human; D000077297:Pregnane X Receptor; D050828:Protein Inhibitors of Activated STAT; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D050796:STAT3 Transcription Factor