iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia

被引：85

作者：

Chikh, Anissa ^{[1
]}

Matin, Rubeta N. H. ^{[1
]}

Senatore, Valentina ^{[1
]}

Hufbauer, Martin ^{[2
]}

Lavery, Danielle ^{[1
]}

Raimondi, Claudio ^{[3
]}

Ostano, Paola ^{[4
]}

Mello-Grand, Maurizia ^{[4
]}

Ghimenti, Chiara ^{[4
]}

Bahta, Adiam ^{[1
]}

Khalaf, Sahira ^{[5
]}

Akguel, Baki ^{[2
]}

Braun, Kristin M. ^{[1
]}

Chiorino, Giovanna ^{[4
]}

Philpott, Michael P. ^{[1
]}

Harwood, Catherine A. ^{[1
]}

Bergamaschi, Daniele ^{[1
]}

机构：

[1] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Ctr Cutaneous Res, London E1 2AT, England

[2] Univ Cologne, Inst Virol, Cologne, Germany

[3] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Dept Diabet, London E1 2AT, England

[4] Fdn Edo & Elvo Tempia Valenta, Canc Genom Lab, Biella, Italy

[5] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Dept Surg, London E1 2AT, England

来源：

EMBO JOURNAL | 2011年 / 30卷 / 20期

关键词：

differentiation; iASPP; miRNA; proliferation; p63; RIGHT-VENTRICULAR CARDIOMYOPATHY; KERATINOCYTE STEM-CELLS; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; NAXOS-DISEASE; EPIDERMAL DIFFERENTIATION; RECESSIVE MUTATION; P63; DEFICIENCY; P53; HOMOLOG; DESMOPLAKIN;

D O I：

10.1038/emboj.2011.302

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4261 / 4273

页数：13

共 54 条

[1] A recessive mutation in desmoplakin causes arrhythmogenic right ventricular dysplasia, skin disorder, and woolly hair [J].