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The C-terminus of p63 contains multiple regulatory elements with different functions

The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms c...

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Autores principales: Straub, W E, Weber, T A, Schäfer, B, Candi, E, Durst, F, Ou, H D, Rajalingam, K, Melino, G, Dötsch, V
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032508/
https://www.ncbi.nlm.nih.gov/pubmed/21364624
http://dx.doi.org/10.1038/cddis.2009.1
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author Straub, W E
Weber, T A
Schäfer, B
Candi, E
Durst, F
Ou, H D
Rajalingam, K
Melino, G
Dötsch, V
author_facet Straub, W E
Weber, T A
Schäfer, B
Candi, E
Durst, F
Ou, H D
Rajalingam, K
Melino, G
Dötsch, V
author_sort Straub, W E
collection PubMed
description The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ∼13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63.
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spelling pubmed-30325082011-02-24 The C-terminus of p63 contains multiple regulatory elements with different functions Straub, W E Weber, T A Schäfer, B Candi, E Durst, F Ou, H D Rajalingam, K Melino, G Dötsch, V Cell Death Dis Original Article The transcription factor p63 is expressed as at least six different isoforms, of which two have been assigned critical biological roles within ectodermal development and skin stem cell biology on the one hand and supervision of the genetic stability of oocytes on the other hand. These two isoforms contain a C-terminal inhibitory domain that negatively regulates their transcriptional activity. This inhibitory domain contains two individual components: one that uses an internal binding mechanism to interact with and mask the transactivation domain and one that is based on sumoylation. We have carried out an extensive alanine scanning study to identify critical regions within the inhibitory domain. These experiments show that a stretch of ∼13 amino acids is crucial for the binding function. Further, investigation of transcriptional activity and the intracellular level of mutants that cannot be sumoylated suggests that sumoylation reduces the concentration of p63. We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63. Nature Publishing Group 2010-01 2010-01-14 /pmc/articles/PMC3032508/ /pubmed/21364624 http://dx.doi.org/10.1038/cddis.2009.1 Text en Copyright © 2009 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This article is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 license. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Straub, W E
Weber, T A
Schäfer, B
Candi, E
Durst, F
Ou, H D
Rajalingam, K
Melino, G
Dötsch, V
The C-terminus of p63 contains multiple regulatory elements with different functions
title The C-terminus of p63 contains multiple regulatory elements with different functions
title_full The C-terminus of p63 contains multiple regulatory elements with different functions
title_fullStr The C-terminus of p63 contains multiple regulatory elements with different functions
title_full_unstemmed The C-terminus of p63 contains multiple regulatory elements with different functions
title_short The C-terminus of p63 contains multiple regulatory elements with different functions
title_sort c-terminus of p63 contains multiple regulatory elements with different functions
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032508/
https://www.ncbi.nlm.nih.gov/pubmed/21364624
http://dx.doi.org/10.1038/cddis.2009.1
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