MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.

Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of...

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Autores principales: Magnus L Hansson, Stefanie Behmer, Rebecca Ceder, Sadollah Mohammadi, Giulio Preta, Roland C Grafström, Bengt Fadeel, Annika E Wallberg
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:ad797bafaafa428db0051574225f02dd2021-11-18T07:04:10ZMAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.1932-620310.1371/journal.pone.0046001https://doaj.org/article/ad797bafaafa428db0051574225f02dd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029358/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of Notch by p300. In this study, we show that MAML1 strongly induced acetylation of the transcription factor early growth response-1 (EGR1) by p300, and increased EGR1 protein expression in embryonic kidney cells. EGR1 mRNA transcripts were also upregulated in the presence of MAML1. We show that MAML1 physically interacted with, and acted cooperatively with EGR1 to increase transcriptional activity of the EGR1 and p300 promoters, which both contain EGR1 binding sites. Bioinformatics assessment revealed a correlation between p300, EGR1 and MAML1 copy number and mRNA alterations in renal clear cell carcinoma and p300, EGR1 and MAML1 gene alterations were associated with increased overall survival. Our findings suggest MAML1 may be a component of the transcriptional networks which regulate EGR1 target genes during nephrogenesis and could also have implications for the development of renal cell carcinoma.Magnus L HanssonStefanie BehmerRebecca CederSadollah MohammadiGiulio PretaRoland C GrafströmBengt FadeelAnnika E WallbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46001 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Magnus L Hansson
Stefanie Behmer
Rebecca Ceder
Sadollah Mohammadi
Giulio Preta
Roland C Grafström
Bengt Fadeel
Annika E Wallberg
MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
description Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of Notch by p300. In this study, we show that MAML1 strongly induced acetylation of the transcription factor early growth response-1 (EGR1) by p300, and increased EGR1 protein expression in embryonic kidney cells. EGR1 mRNA transcripts were also upregulated in the presence of MAML1. We show that MAML1 physically interacted with, and acted cooperatively with EGR1 to increase transcriptional activity of the EGR1 and p300 promoters, which both contain EGR1 binding sites. Bioinformatics assessment revealed a correlation between p300, EGR1 and MAML1 copy number and mRNA alterations in renal clear cell carcinoma and p300, EGR1 and MAML1 gene alterations were associated with increased overall survival. Our findings suggest MAML1 may be a component of the transcriptional networks which regulate EGR1 target genes during nephrogenesis and could also have implications for the development of renal cell carcinoma.
format article
author Magnus L Hansson
Stefanie Behmer
Rebecca Ceder
Sadollah Mohammadi
Giulio Preta
Roland C Grafström
Bengt Fadeel
Annika E Wallberg
author_facet Magnus L Hansson
Stefanie Behmer
Rebecca Ceder
Sadollah Mohammadi
Giulio Preta
Roland C Grafström
Bengt Fadeel
Annika E Wallberg
author_sort Magnus L Hansson
title MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
title_short MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
title_full MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
title_fullStr MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
title_full_unstemmed MAML1 acts cooperatively with EGR1 to activate EGR1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
title_sort maml1 acts cooperatively with egr1 to activate egr1-regulated promoters: implications for nephrogenesis and the development of renal cancer.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/ad797bafaafa428db0051574225f02dd
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