Nucleic Acids Research Advance Access published online on September 8, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp724
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Gene Regulation, Chromatin and Epigenetics |
GSK3β is a negative regulator of the transcriptional coactivator MAML1
ciborDepartment of Biosciences and Nutrition, Karolinska Institutet, 141 86 Stockholm, Sweden
*To whom correspondence should be addressed. Tel: +46 8 58583951; Fax: +46 8 7116659; Email: annika.wallberg{at}ki.se
Received April 14, 2009. Revised August 4, 2009. Accepted August 17, 2009.
Glycogen synthase kinase 3β (GSK3β) is involved in several cellular signaling systems through regulation of the activity of diverse transcription factors such as Notch, p53 and β-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, β-catenin and MEF2C. In this report, we show that active GSK3β directly interacts with the MAML1 N-terminus and decreases MAML1 transcriptional activity, suggesting that GSK3β 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 GSK3β to nuclear bodies; this function requires full-length MAML1 protein.
The authors wish it to be known that, in their opinion, the first and second authors should be regarded as joint First Authors.