title: GSK3beta is a negative regulator of the transcriptional coactivator MAML1.
abstract: Glycogen synthase kinase 3beta (GSK3beta) is involved in several cellular signaling systems through regulation of the activity of diverse transcription factors such as Notch, p53 and beta-catenin. Mastermind-like 1 (MAML1) was originally identified as a Notch coactivator, but has also been reported to function as a transcriptional coregulator of p53, beta-catenin and MEF2C. In this report, we show that active GSK3beta directly interacts with the MAML1 N-terminus and decreases MAML1 transcriptional activity, suggesting that GSK3beta might target a coactivator in its regulation of gene expression. We have previously shown that MAML1 increases global acetylation of histones, and here we show that the GSK3 inhibitor SB41, further enhances MAML1-dependent histone acetylation in cells. Finally, MAML1 translocates GSK3beta to nuclear bodies; this function requires full-length MAML1 protein.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Mariana
authors.initials: M
authors.lastname: Saint Just Ribeiro
authors.forename: Magnus L
authors.initials: ML
authors.lastname: Hansson
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Lindberg
authors.forename: Anita E
authors.initials: AE
authors.lastname: Popko-Scibor
authors.forename: Annika E
authors.initials: AE
authors.lastname: Wallberg
mesh_terms: D000107:Acetylation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006657:Histones / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C430872:MAML1 protein, human; D051881:Receptor, Notch1; D014157:Transcription Factors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3