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Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling

Early studies demonstrated the involvement of ubiquitination of the Notch intracellular domain for rapid turnover of the transcriptional complex at Notch target genes. It was shown that this ubiquitination was promoted by the co-activator Mastermind like 1 (MAML1). MAML1 also contains numerous lysin...

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Autores principales: Farshbaf, Mozhgan, Lindberg, Mikael J., Truong, Anh, Bevens, Zachery, Chambers, Elaina, Pournara, Angeliki, Wallberg, Annika E., White, J. Brandon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520489/
https://www.ncbi.nlm.nih.gov/pubmed/26225565
http://dx.doi.org/10.1371/journal.pone.0134013
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author Farshbaf, Mozhgan
Lindberg, Mikael J.
Truong, Anh
Bevens, Zachery
Chambers, Elaina
Pournara, Angeliki
Wallberg, Annika E.
White, J. Brandon
author_facet Farshbaf, Mozhgan
Lindberg, Mikael J.
Truong, Anh
Bevens, Zachery
Chambers, Elaina
Pournara, Angeliki
Wallberg, Annika E.
White, J. Brandon
author_sort Farshbaf, Mozhgan
collection PubMed
description Early studies demonstrated the involvement of ubiquitination of the Notch intracellular domain for rapid turnover of the transcriptional complex at Notch target genes. It was shown that this ubiquitination was promoted by the co-activator Mastermind like 1 (MAML1). MAML1 also contains numerous lysine residues that may also be ubiquitinated and necessary for protein regulation. In this study, we show that over-expressed MAML1 is ubiquitinated and identify eight conserved lysine residues which are required for ubiquitination. We also show that p300 stimulates ubiquitination and that Notch inhibits ubiquitination. Furthermore, we show that a mutant MAML1 that has decreased ubiquitination shows increased output from a HES1 reporter gene assay. Therefore, we speculate that ubiquitination of MAML1 might be a mechanism to maintain low levels of the protein until needed for transcriptional activation. In summary, this study identifies that MAML1 is ubiquitinated in the absence of Notch signaling to maintain low levels of MAML1 in the cell. Our data supports the notion that a precise and tight regulation of the Notch pathway is required for this signaling pathway.
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spelling pubmed-45204892015-08-06 Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling Farshbaf, Mozhgan Lindberg, Mikael J. Truong, Anh Bevens, Zachery Chambers, Elaina Pournara, Angeliki Wallberg, Annika E. White, J. Brandon PLoS One Research Article Early studies demonstrated the involvement of ubiquitination of the Notch intracellular domain for rapid turnover of the transcriptional complex at Notch target genes. It was shown that this ubiquitination was promoted by the co-activator Mastermind like 1 (MAML1). MAML1 also contains numerous lysine residues that may also be ubiquitinated and necessary for protein regulation. In this study, we show that over-expressed MAML1 is ubiquitinated and identify eight conserved lysine residues which are required for ubiquitination. We also show that p300 stimulates ubiquitination and that Notch inhibits ubiquitination. Furthermore, we show that a mutant MAML1 that has decreased ubiquitination shows increased output from a HES1 reporter gene assay. Therefore, we speculate that ubiquitination of MAML1 might be a mechanism to maintain low levels of the protein until needed for transcriptional activation. In summary, this study identifies that MAML1 is ubiquitinated in the absence of Notch signaling to maintain low levels of MAML1 in the cell. Our data supports the notion that a precise and tight regulation of the Notch pathway is required for this signaling pathway. Public Library of Science 2015-07-30 /pmc/articles/PMC4520489/ /pubmed/26225565 http://dx.doi.org/10.1371/journal.pone.0134013 Text en © 2015 Farshbaf et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Farshbaf, Mozhgan
Lindberg, Mikael J.
Truong, Anh
Bevens, Zachery
Chambers, Elaina
Pournara, Angeliki
Wallberg, Annika E.
White, J. Brandon
Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title_full Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title_fullStr Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title_full_unstemmed Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title_short Mastermind-Like 1 Is Ubiquitinated: Functional Consequences for Notch Signaling
title_sort mastermind-like 1 is ubiquitinated: functional consequences for notch signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520489/
https://www.ncbi.nlm.nih.gov/pubmed/26225565
http://dx.doi.org/10.1371/journal.pone.0134013
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