Identification of New Human Mastermind Proteins Defines a Family That Consists of Positive Regulators for Notch Signaling

Lin, Sey‐En; Oyama, Toshinao; Nagase, Takahiro; Harigaya, Kenichi; Kitagawa, Motoo

doi:10.1074/jbc.m209529200

Cited by 92 publications

(116 citation statements)

References 46 publications

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“…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).…”

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 97%

“…The Mastermind homologues have been identified in Drosophila (Yedvobnick et al, 1988;Smoller et al, 1990), C. elegans (Petcherski and Kimble, 2000b), Xenopus (Katada and Kinoshita, 2003), mouse (Petcherski and Kimble, 2000b; and human (Wu et al, 2000(Wu et al, , 2002Kitagawa et al, 2001;Lin et al, 2002). The Mastermind (mam) gene first was identified in Drosophila as one of the original group of 'neurogenic' loci along with Notch, and loss of the function of Mam resulted in excessive neural cells at the expense of epithelial cells (Yedvobnick et al, 1988;, indicating that the molecule regulated neuronal cell-fate decisions.…”

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

“…Biochemically, all MAML proteins appear to form stable DNA-binding complexes with ICNs and the transcription factor CSL upon Notch activation (Lin et al, 2002;Wu et al, 2002) and potentiate transcription of Notch target genes. These data led to a model in which MAML proteins are recruited to Notch/CSL on the target gene promoters when Notch receptors are activated, contributing to transcriptional activation.…”

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

“…Although more studies have investigated MAML1, it has been determined that both MAML2 and MAML3 interact with Notch receptors and also interact with p300 (Lin et al, 2002;Wu et al, 2002;L Wu et al, unpublished). Additional interacting proteins have not yet been identified.…”

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

See 3 more Smart Citations

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

2008

Oncogene

137

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Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 97%

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

Section: Identification Of Maml Proteins and Investigations Into Theimentioning

confidence: 99%

See 2 more Smart Citations

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

2008

Oncogene

137

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“…These two proteins are structurally and functionally related to MAML3 (29,30). However, MAML1 and MAML2 expression in SK-N-SH and SH-SY5Y cells did not mediate resistance to RA (Fig.…”

Section: Overexpression Of Maml3 Confers Resistance To Ra In Multiplementioning

confidence: 99%

Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma

Heynen

Nevedomskaya

Palit

et al. 2016

Molecular Cancer Research

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Neuroblastoma cell lines can differentiate upon treatment with retinoic acid (RA), a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen, we identified an unexpected link between RA signaling and mastermindlike 3 (MAML3), a known transcriptional coactivator for NOTCH. Our findings indicate that MAML3 expression leads to the loss of activation of a subset of RA target genes, which hampers RA-induced differentiation and promotes resistance to RA. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the RA receptor, suggesting a direct role for MAML3 in the regulation of these genes. In addition, MAML3 has RA-independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. These results demonstrate an important mechanistic role for MAML3 in proliferation and RA-mediated differentiation.Implications: MAML3 coordinates transcription regulation with receptor tyrosine kinase pathway activation, shedding new light on why this gene is mutated in multiple cancers.

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Clear cell hidradenoma of the skin—a third tumor type with a t(11;19)‐associated TORC1–MAML2 gene fusion

Behboudi

Winnes

Gorunova

et al. 2005

Genes Chromosomes & Cancer

100

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Recent studies have shown that the t(11;19)(q21;p13) translocation in mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the N-terminal CREB-binding domain of the cAMP coactivator TORC1 (a.k.a. MECT1 and WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type, clear cell hidradenoma of the skin, also expresses this gene fusion. RT-PCR analysis of a clear cell hidradenoma with a t(11;19)(q21;p13) translocation revealed expression of a TORC1-MAML2 fusion transcript consisting of exon 1 of TORC1 fused to exons 2-5 of MAML2. Because the fusion was only detected in a single case, the frequency of this aberration in clear cell hidradenomas remains unknown. These results demonstrate that the t(11;19) in mucoepidermoid carcinoma, Warthin's tumor, and clear cell hidradenoma targets the same genes and results in identical gene fusions, indicating that at least subgroups of these glandular tumors evolve through activation of the same molecular pathways.

show abstract

Identification of New Human Mastermind Proteins Defines a Family That Consists of Positive Regulators for Notch Signaling

Cited by 92 publications

References 46 publications

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

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

Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma

Clear cell hidradenoma of the skin—a third tumor type with a t(11;19)‐associated TORC1–MAML2 gene fusion

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