GSK3beta is a negative regulator of the transcriptional coactivator MAML1.
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.
Saint Just Ribeiro
Mariana
M
Department of Biosciences and Nutrition, Karolinska Institutet, 141 86 Stockholm, Sweden.
Hansson
Magnus L
ML
Lindberg
Mikael J
MJ
Popko-Scibor
Anita E
AE
Wallberg
Annika E
AE
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
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