Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex

Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways

“…Finally, crystal structure analyses of the Notch core complex confirmed that the interaction of ICN and CSL creates the recruitment site for MAML proteins (Nam et al, 2006;Wilson and Kovall, 2006). Mechanistically, MAML1 is required for chromatin-dependent transactivation by the reconstituted Notch ICN-CSL enhancer complex in vitro (Fryer et al, 2002;Wallberg et al, 2002).…”

“…Our group and others previously identified a family of three mammalian MAML co-activators as essential regulators of Notch-induced transcriptional events (Wu et al, 2000(Wu et al, , 2002Petcherski and Kimble, 2000a;Fryer et al, 2002;Lin et al, 2002;Wu and Griffin, 2004). The three human MAML genes encode nuclear proteins and have limited sequence homology with their othologues, yet are highly conserved in their structure ( Figure 1b).…”

“…(1) TAD1 is located in the region of aa 75-300 of MAML1, and contains a p300/CBP-binding site. Thus, MAML1 recruits the chromatin modification enzyme p300/CBP and leads to nucleosome acetylation at Notch enhancers to activate transcription in vitro (Fryer et al, 2002). However, the recruitment of p300/CBP is not sufficient to activate the transcription of Notch target genes in vivo, because an MAML1 mutant, MAML1 (1-302) containing TAD1 and retaining the p300 binding activity failed to activate Notch target genes and actually interfered with Notch signaling in vivo (Wu et al, 2000).…”

Variants in Notch signalling pathway genes, PSEN1 and MAML2, predict overall survival in Chinese patients with epithelial ovarian cancer

“…The MAML2 protein contains a conserved basic domain that could bind to the ankyrin repeat domain of the intracellular domain of the Notch receptors (ICN1‐4) in their N‐terminus. The protein binds to an extended groove that is formed by the interaction of CBF1, suppressor of Hairless, LAG‐1 with ICN, which could positively regulate the Notch signalling pathway 34, 35. In fact, the translocation of MAML2 could create a fusion oncogene MECT1 / MAML2 , which could be involved in the process of disrupting the normal cell cycle, differentiation and tumour development, exerting an oncogenic role in mucoepidermoid carcinoma 36.…”

Heterogeneity of Jagged1 expression in human and mouse intestinal tumors: implications for targeting Notch signaling

“…Upon ligand binding, Notch receptors are ultimately cleaved by a g-secretase, which releases Notch intracellular domain (NICD) from the plasma membrane and initiates its subsequent translocation into the nucleus. Once there, NICD activates the expression of downstream target genes (Fryer et al, 2002) by binding to the conserved transcription factor, RBP-Jk (Fortini and Artavanis-Tsakonas, 1994), among whose targets are the Hes (Hairy Enhancer of Split) basic helix-loop-helix transcriptional repressor family. In particular, NICD stimulates the expression of Hes1 (Jarriault et al, 1995), which represses the activity of Math1 (or Hath1, its human homologue) (Zheng et al, 2000;Yang et al, 2001).…”