title: Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation.
abstract: Pax proteins are DNA-binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The Pax2 gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c-Jun N-terminal kinase (JNK) to enhance Pax2-dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Brophy
authors.forename: Inna
authors.initials: I
authors.lastname: Levitan
authors.forename: Stefano
authors.initials: S
authors.lastname: Stifani
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Dressler
mesh_terms: D019943:Amino Acid Substitution; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D051762:PAX2 Transcription Factor; D010766:Phosphorylation; D010957:Plasmids; D012097:Repressor Proteins / Q000378:metabolism*; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D051762:PAX2 Transcription Factor; D012097:Repressor Proteins; D014157:Transcription Factors; C497318:PAX2 protein, human; C091023:gro protein, Drosophila