Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.

The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15(Ink4)), cdkn1a (p21(Cip1)), and cdkn1c (p57(Kip2)). Whether Miz1-mediated repression...

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Autores principales:	Jan Hönnemann, Adrián Sanz-Moreno, Elmar Wolf, Martin Eilers, Hans-Peter Elsässer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31a3131ec12347d2b0d60793087004fa
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spelling	oai:doaj.org-article:31a3131ec12347d2b0d60793087004fa2021-11-18T07:22:37ZMiz1 is a critical repressor of cdkn1a during skin tumorigenesis.1932-620310.1371/journal.pone.0034885https://doaj.org/article/31a3131ec12347d2b0d60793087004fa2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22509363/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15(Ink4)), cdkn1a (p21(Cip1)), and cdkn1c (p57(Kip2)). Whether Miz1-mediated repression is important for control of cell proliferation in vivo and for tumor formation is unknown. Here we show that deletion of the Miz1 POZ domain, which is critical for Miz1 function, restrains the development of skin tumors in a model of chemically-induced, Ras-dependent tumorigenesis. While the stem cell compartment appears unaffected, interfollicular keratinocytes lacking functional Miz1 exhibit a reduced proliferation and an accelerated differentiation of the epidermis in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Tumorigenesis, proliferation and normal differentiation are restored in animals lacking cdkn1a, but not in those lacking cdkn2b. Our data demonstrate that Miz1-mediated attenuation of cell cycle arrest pathways via repression of cdkn1a has a critical role during tumorigenesis in the skin.Jan HönnemannAdrián Sanz-MorenoElmar WolfElmar WolfMartin EilersHans-Peter ElsässerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34885 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jan Hönnemann Adrián Sanz-Moreno Elmar Wolf Elmar Wolf Martin Eilers Hans-Peter Elsässer Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
description	The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15(Ink4)), cdkn1a (p21(Cip1)), and cdkn1c (p57(Kip2)). Whether Miz1-mediated repression is important for control of cell proliferation in vivo and for tumor formation is unknown. Here we show that deletion of the Miz1 POZ domain, which is critical for Miz1 function, restrains the development of skin tumors in a model of chemically-induced, Ras-dependent tumorigenesis. While the stem cell compartment appears unaffected, interfollicular keratinocytes lacking functional Miz1 exhibit a reduced proliferation and an accelerated differentiation of the epidermis in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Tumorigenesis, proliferation and normal differentiation are restored in animals lacking cdkn1a, but not in those lacking cdkn2b. Our data demonstrate that Miz1-mediated attenuation of cell cycle arrest pathways via repression of cdkn1a has a critical role during tumorigenesis in the skin.
format	article
author	Jan Hönnemann Adrián Sanz-Moreno Elmar Wolf Elmar Wolf Martin Eilers Hans-Peter Elsässer
author_facet	Jan Hönnemann Adrián Sanz-Moreno Elmar Wolf Elmar Wolf Martin Eilers Hans-Peter Elsässer
author_sort	Jan Hönnemann
title	Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
title_short	Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
title_full	Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
title_fullStr	Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
title_full_unstemmed	Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
title_sort	miz1 is a critical repressor of cdkn1a during skin tumorigenesis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/31a3131ec12347d2b0d60793087004fa
work_keys_str_mv	AT janhonnemann miz1isacriticalrepressorofcdkn1aduringskintumorigenesis AT adriansanzmoreno miz1isacriticalrepressorofcdkn1aduringskintumorigenesis AT elmarwolf miz1isacriticalrepressorofcdkn1aduringskintumorigenesis AT elmarwolf miz1isacriticalrepressorofcdkn1aduringskintumorigenesis AT martineilers miz1isacriticalrepressorofcdkn1aduringskintumorigenesis AT hanspeterelsasser miz1isacriticalrepressorofcdkn1aduringskintumorigenesis
_version_	1718423526570983424

Miz1 is a critical repressor of cdkn1a during skin tumorigenesis.

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