SUMO modification regulates the transcriptional activity of MAML1.
The Mastermindlike (MAML) family, comprising human MAML1, MAML2, and MAML3, are transcriptional regulators in Notch signaling. MAML proteins contain two consensus sites for SUMOylation at Lysine217 and Lysine299 that are conserved in humans, mice, and Xenopus. In this report, we show that MAML1 is SUMOylated at both sites. The E2-conjugating enzyme UBC9 is essential for MAML1 SUMOylation, and the E3 ligase PIAS1 stimulates this activity. Mutation of the lysines abolishes SUMOylation of MAML1 and strongly increases MAML1-activated transcription in cell culture assays. The protease SENP1 reverses SUMOylation of MAML1 and potentiates the transcription factor activity of MAML1. Furthermore, SUMOylation enhances MAML1 interaction with HDAC7, which decreases MAML1 transcriptional activity. Taken together, our data indicate that SUMOylation of MAML1 is a mechanism for repressing MAML1 activity by influencing its interaction with HDAC7.
Lindberg
Mikael J
MJ
Department of Biosciences and Nutrition, Halsovagen 7-9, Karolinska Institutet, 141 86 Stockholm, Sweden.
Popko-Scibor
Anita E
AE
Hansson
Magnus L
ML
Wallberg
Annika E
AE
D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins; D011499:Protein Processing, Post-Translational; D025842:SUMO-1 Protein / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C430872:MAML1 protein, human; C471297:MAML2 protein, human; C471298:MAML3 protein, human; D009687:Nuclear Proteins; D025842:SUMO-1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; C543273:HDAC7 protein, human; D006655:Histone Deacetylases