A proline repeat domain in the Notch co-activator MAML1 is important for p300-mediated acetylation of MAML1

Mariana Saint Just Ribeiro , Magnus L Hansson , Annika E Wallberg (1)

1 Department of Biosciences and Nutrition

Ligand activation of Notch leads to the release of the intracellular receptor domain (Notch IC), which translocates to the nucleus and interacts with the DNA-binding protein CSL to control expression of specific target genes. In addition to ligand-mediated activation, Notch signaling can be further modulated by interactions of Notch IC with a number of other proteins. MAML1 (Mastermind like-1) has previously been shown to act cooperatively with the histone acetyltransferase p300 in Notch IC-mediated transcription. In this report we show that the N-terminal domain of MAML1 directly interacts with both p300 and histones, and the p300-MAML1 complex specifically acetylates histone H3 and H4 tails in chromatin. Furthermore, p300 acetylates MAML1, and evolutionary conserved lysines in the MAML1 N-terminus are direct substrates for p300-mediated acetylation. The N-terminal domain of MAML1 contains a proline repeat motif (PXPAAPAP) that previously has been shown to be present in p53 and important for the p300-p53 interaction. We show that the MAML1 proline repeat motif interacts with p300 and enhances the activity of the MAML1 N-terminus in vivo. These findings suggest that the N-terminal domain of MAML1 plays an important role in Notch regulated transcription, by direct interactions with both Notch, p300 and histones.

Mots clés: Life Sciences

Mariana Saint Just Ribeiro, Magnus L Hansson, Annika E Wallberg. A proline repeat domain in the Notch co-activator MAML1 is important for p300-mediated acetylation of MAML1. Biochemical Journal, 2007, 404 (2), pp.289-298. ⟨10.1042/BJ20061900⟩. ⟨hal-00478726⟩