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A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer

Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strict...

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Autores principales: Zema, Sabrina, Pelullo, Maria, Nardozza, Francesca, Felli, Maria Pia, Screpanti, Isabella, Bellavia, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787167/
https://www.ncbi.nlm.nih.gov/pubmed/33425921
http://dx.doi.org/10.3389/fcell.2020.613557
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author Zema, Sabrina
Pelullo, Maria
Nardozza, Francesca
Felli, Maria Pia
Screpanti, Isabella
Bellavia, Diana
author_facet Zema, Sabrina
Pelullo, Maria
Nardozza, Francesca
Felli, Maria Pia
Screpanti, Isabella
Bellavia, Diana
author_sort Zema, Sabrina
collection PubMed
description Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strictly controlled by the assembly of multiprotein complexes into the nucleus, where a regulated recruitment of specific transcription factors and coactivators on gene promoter region leads to different transcriptional outcomes. MAML1 results to be a versatile coactivator, able to set up synergistic interlinking with pivotal signaling cascades and able to coordinate the network of cross-talking pathways. Accordingly, despite its original identification as a component of the Notch signaling pathway, several recent reports suggest a more articulated role for MAML1 protein, showing that it is able to sustain/empower Wnt/β-catenin, Hh and Hippo pathways, in a Notch-independent manner. For this reason, MAML1 may be associated to a molecular “switch”, with the function to control the activation of major signaling pathways, triggering in this way critical biological processes during embryonic and post-natal life. In this review, we summarize the current knowledge about the pleiotropic role played by MAML proteins, in particular MAML1, and we recapitulate how it takes part actively in physiological and pathological signaling networks. On this point, we also discuss the contribution of MAML proteins to malignant transformation. Accordingly, genetic alterations or impaired expression of MAML proteins may lead to a deregulated crosstalk among the pathways, culminating in a series of pathological disorders, including cancer development. Given their central role, a better knowledge of the molecular mechanisms that regulate the interplay of MAML proteins with several signaling pathways involved in tumorigenesis may open up novel opportunities for an attractive molecular targeted anticancer therapy.
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spelling pubmed-77871672021-01-07 A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer Zema, Sabrina Pelullo, Maria Nardozza, Francesca Felli, Maria Pia Screpanti, Isabella Bellavia, Diana Front Cell Dev Biol Cell and Developmental Biology Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strictly controlled by the assembly of multiprotein complexes into the nucleus, where a regulated recruitment of specific transcription factors and coactivators on gene promoter region leads to different transcriptional outcomes. MAML1 results to be a versatile coactivator, able to set up synergistic interlinking with pivotal signaling cascades and able to coordinate the network of cross-talking pathways. Accordingly, despite its original identification as a component of the Notch signaling pathway, several recent reports suggest a more articulated role for MAML1 protein, showing that it is able to sustain/empower Wnt/β-catenin, Hh and Hippo pathways, in a Notch-independent manner. For this reason, MAML1 may be associated to a molecular “switch”, with the function to control the activation of major signaling pathways, triggering in this way critical biological processes during embryonic and post-natal life. In this review, we summarize the current knowledge about the pleiotropic role played by MAML proteins, in particular MAML1, and we recapitulate how it takes part actively in physiological and pathological signaling networks. On this point, we also discuss the contribution of MAML proteins to malignant transformation. Accordingly, genetic alterations or impaired expression of MAML proteins may lead to a deregulated crosstalk among the pathways, culminating in a series of pathological disorders, including cancer development. Given their central role, a better knowledge of the molecular mechanisms that regulate the interplay of MAML proteins with several signaling pathways involved in tumorigenesis may open up novel opportunities for an attractive molecular targeted anticancer therapy. Frontiers Media S.A. 2020-12-21 /pmc/articles/PMC7787167/ /pubmed/33425921 http://dx.doi.org/10.3389/fcell.2020.613557 Text en Copyright © 2020 Zema, Pelullo, Nardozza, Felli, Screpanti and Bellavia. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zema, Sabrina
Pelullo, Maria
Nardozza, Francesca
Felli, Maria Pia
Screpanti, Isabella
Bellavia, Diana
A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title_full A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title_fullStr A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title_full_unstemmed A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title_short A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer
title_sort dynamic role of mastermind-like 1: a journey through the main (path)ways between development and cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787167/
https://www.ncbi.nlm.nih.gov/pubmed/33425921
http://dx.doi.org/10.3389/fcell.2020.613557
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