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

As, McElhinny; Li, Jian‐Liang; Wu, Linquan

doi:10.1038/onc.2008.228

Cited by 133 publications

(95 citation statements)

References 61 publications

(81 reference statements)

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“…However, Mef2c is a crucial muscle-specific transcription factor, which is not expressed in K14-positive epithelial cells. Both Maml1/p53 and Maml1/NF-B interactions involve the N-terminal region of Maml1 (amino acids 72-301) (McElhinny et al, 2008;Jin et al, 2010), which is not present in the dnMaml1. Likewise, -catenin binds to the C-terminal region of Maml1 (amino acids 640-1016) (Alves-Guerra et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity

et al. 2013

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SUMMARYConjunctival goblet cells primarily synthesize mucins to lubricate the ocular surface, which is essential for normal vision. Notch signaling has been known to associate with goblet cell differentiation in intestinal and respiratory tracts, but its function in ocular surface has yet to be fully characterized. Herein, we demonstrate that conditional inhibition of canonical Notch signaling by expressing dominant negative mastermind-like 1 (dnMaml1) in ocular surface epithelia resulted in complete suppression of goblet cell differentiation during and subsequent to development. When compared with the ocular surface of wild-type mice (OS Wt ), expression of dnMaml1 at the ocular surface (OS dnMaml1 ) caused conjunctival epithelial hyperplasia, aberrant desquamation, failure of Mucin 5ac (Muc5ac) synthesis, subconjunctival inflammation and epidermal metaplasia in cornea. In addition, conditional deletion of Notch1 from the ocular surface epithelia partially recapitulated OS dnMaml1 phenotypes. We have demonstrated that N1-ICD (Notch1 intracellular domain) transactivated the mouse Krüppel-like factor 4 (Klf) promoter and that Klf4 directly bound to and significantly potentiated the Muc5ac promoter. By contrast, OS dnMaml1 dampened Klf4 and Klf5 expression, and diminished Muc5ac synthesis. Collectively, these findings indicated that Maml-mediated Notch signaling plays a pivotal role in the initiation and maintenance of goblet cell differentiation for normal ocular surface morphogenesis and homeostasis through regulation of Klf4 and Klf5.

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Section: Discussionmentioning

confidence: 99%

Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity

et al. 2013

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“…There are currently very few reports of Notch-independent roles of Mam proteins (McElhinny et al, 2008). In two cases, the mammalian Mam homolog MAML1 was shown to bind and collaborate with DNA-binding proteins (p53 and MEF2C) other than those of the Su(H) family.…”

Section: Does Mam Have a Direct Role In Fsc Hh Signaling?mentioning

confidence: 99%

“…Mam has long been considered to be a dedicated co-activator in the Notch signaling pathway, because genetic analyses in Drosophila and other model organisms generally show a congruence between Notch and Mam loss-of-function phenotypes (Bray, 2006;McElhinny et al, 2008). Biochemically, Mam binds to a composite surface contributed by the cleaved intracellular domain of activated Notch and the DNA-binding protein Su(H), and provides an essential transcriptional activation function that includes the recruitment of CREB-Binding Protein (CBP) (Fryer et al, 2002;Wallberg et al, 2002 …”

Section: Mam Function In Fsc Is Independent Of Notch Signalingmentioning

confidence: 99%

Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind

Vied

Kalderon

2009

Development

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Normal self-renewal of follicle stem cells (FSCs) in the Drosophila ovary requires Hedgehog (Hh) signaling. Excess Hh signaling, induced by loss of patched (ptc), causes cell-autonomous duplication of FSCs. We have used a genetic screen to identify Mastermind (Mam), the Notch pathway transcriptional co-activator, as a rare dose-dependent modifier of aberrant FSC expansion induced by excess Hh. Complete loss of Mam activity severely compromises the persistence of both normal and ptc mutant FSCs, but does not affect the maintenance of ovarian germline stem cells. Thus, Mam, like Hh, is a crucial stem cell factor that acts selectively on FSCs in the ovary. Surprisingly, other Notch pathway components, including Notch itself, are not similarly required for FSC maintenance. Furthermore, excess Notch pathway activity alone accelerates FSC loss and cannot ameliorate the more severe defects of mam mutant FSCs. This suggests an unconventional role for Mam in FSCs that is independent of Notch signaling. Loss of Mam reduces the expression of a Hh pathway reporter in FSCs but not in wing discs, suggesting that Mam might enhance Hh signaling specifically in stem cells of the Drosophila ovary.

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“…Exploring MAML functions in other signaling pathways like Wnt and p53 can prove to be of therapeutic significance. 5 In conclusion, comprehensive expression outlines of the three MAMLs in various tissues and at diverse development phases can help to manipulate and deliver a specific target therapy in oral malignancies.…”

mentioning

confidence: 99%

“…6 It is known to play a role in myogenesis, coactivates p53 required for p53-mediated germ-cell apoptotic response, and β-catenin-based transcriptional events. 5 Yoshida et al 8 have studied the pathological significance of Notch1 and its activation mechanism in the pathogenesis of oral squamous cell carcinoma (OSCC) and found increased expression of Notch1 and NICD with their localization at the invasive tumor front. Moreover, they emphasized the role of MAML family of coactivators in the development and progression of OSCC.…”

mentioning

confidence: 99%

Mastermind-like Gene Family: A New Ray of Hope in Cancer Therapeutics

Nikunj¹

2016

World Journal of Dentistry

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

Cited by 133 publications

References 61 publications

Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity

Mastermind-like transcriptional co-activator-mediated Notch signaling is indispensable for maintaining conjunctival epithelial identity

Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind

Mastermind-like Gene Family: A New Ray of Hope in Cancer Therapeutics

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