Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

被引：328

作者：

Nguyen, BC

Lefort, K

Mandinova, A

Antonini, D

Devgan, V

Della Gatta, G

Koster, MI

Zhang, Z

Wang, J

di Vignano, AT

Kitajewski, J

Chiorino, G

Roop, DR

Missero, C

Dotto, GP ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[2] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[3] Telethon Inst Genet & Med, TIGEM, I-80131 Naples, Italy

[4] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[5] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA

[6] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10032 USA

[7] Columbia Univ, Med Ctr, Irving Canc Res Ctr, New York, NY 10032 USA

[8] Fondo Edo Tempia, Lab Pharmacogen, I-13900 Biella, Italy

来源：

GENES & DEVELOPMENT | 2006年 / 20卷 / 08期

关键词：

keratinocyte; stem cells; Notch; p63; interferon -responsive genes; HES/HERP family members;

D O I：

10.1101/gad.1406006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch 1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.

引用

页码：1028 / 1042

页数：15