Universität zu Köln

Chikh, Anissa ORCID: 0000-0002-4235-3870, Matin, Rubeta N. H., Senatore, Valentina, Hufbauer, Martin, Lavery, Danielle, Raimondi, Claudio ORCID: 0000-0002-1419-6855, Ostano, Paola, Mello-Grand, Maurizia, Ghimenti, Chiara, Bahta, Adiam, Khalaf, Sahira, Akguel, Baki, Braun, Kristin M., Chiorino, Giovanna ORCID: 0000-0002-9502-6400, Philpott, Michael P., Harwood, Catherine A. and Bergamaschi, Daniele ORCID: 0000-0002-3955-1091 (2011). iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. Embo J., 30 (20). S. 4261 - 4274. NEW YORK: NATURE PUBLISHING GROUP. ISSN 0261-4189

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Abstract

iASPP, an inhibitory member of the ASPP (apoptosis stimulating protein of p53) family, is an evolutionarily conserved inhibitor of p53 which is frequently upregulated in human cancers. However, little is known about the role of iASPP under physiological conditions. Here, we report that iASPP is a critical regulator of epithelial development. We demonstrate a novel autoregulatory feedback loop which controls crucial physiological activities by linking iASPP to p63, via two previously unreported microRNAs, miR-574-3p and miR-720. By investigating its function in stratified epithelia, we show that iASPP participates in the p63-mediated epithelial integrity program by regulating the expression of genes essential for cell adhesion. Silencing of iASPP in keratinocytes by RNA interference promotes and accelerates a differentiation pathway, which also affects and slowdown cellular proliferation. Taken together, these data reveal iASPP as a key regulator of epithelial homeostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chikh, Anissa UNSPECIFIED orcid.org/0000-0002-4235-3870 UNSPECIFIED Matin, Rubeta N. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Senatore, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hufbauer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lavery, Danielle UNSPECIFIED UNSPECIFIED UNSPECIFIED Raimondi, Claudio UNSPECIFIED orcid.org/0000-0002-1419-6855 UNSPECIFIED Ostano, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Mello-Grand, Maurizia UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghimenti, Chiara UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahta, Adiam UNSPECIFIED UNSPECIFIED UNSPECIFIED Khalaf, Sahira UNSPECIFIED UNSPECIFIED UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Kristin M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiorino, Giovanna UNSPECIFIED orcid.org/0000-0002-9502-6400 UNSPECIFIED Philpott, Michael P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Harwood, Catherine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergamaschi, Daniele UNSPECIFIED orcid.org/0000-0002-3955-1091 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-487179
DOI:	10.1038/emboj.2011.302
Journal or Publication Title:	Embo J.
Volume:	30
Number:	20
Page Range:	S. 4261 - 4274
Date:	2011
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	0261-4189
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RIGHT-VENTRICULAR CARDIOMYOPATHY; KERATINOCYTE STEM-CELLS; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; NAXOS-DISEASE; EPIDERMAL DIFFERENTIATION; RECESSIVE MUTATION; P63 DEFICIENCY; P53 HOMOLOG; DESMOPLAKIN Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48717