![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
1 Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA; 2 Department of Biochemistry, University of Lausanne, Epalinges 1066 CH, Switzerland; 3 Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy; 4 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA; 5 Department of Pathology, Department of Obstetrics and Gynecology, and Irving Cancer Research Center, Columbia University Medical Center, New York, New York 10032, USA; 6 Laboratory of Cancer Pharmacogenomics, Fondo "Edo Tempia," 13900 Biella, Italy
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 Notch1-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.
[Keywords: Keratinocyte; stem cells; Notch; p63; interferon-responsive genes; HES/HERP family members]
Received December 27, 2005; revised version accepted February 10, 2006.
E-MAIL gdotto{at}partners.org; FAX 41-21-692-5705.
9 E-MAIL missero{at}tigem.it; FAX 39-081-6132351.
Supplemental material is available at http://www.genesdev.org.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1406006
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  I. J. Frew, A. Minola, S. Georgiev, M. Hitz, H. Moch, S. Richard, A. O. Vortmeyer, and W. Krek Combined Vhlh and Pten Mutation Causes Genital Tract Cystadenoma and Squamous Metaplasia Mol. Cell. Biol., July 15, 2008; 28(14): 4536 - 4548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Della Gatta, M. Bansal, A. Ambesi-Impiombato, D. Antonini, C. Missero, and D. di Bernardo Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering Genome Res., June 1, 2008; 18(6): 939 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fuchs Skin stem cells: rising to the surface J. Cell Biol., January 28, 2008; 180(2): 273 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Xin, R. U. Lukacs, D. A. Lawson, D. Cheng, and O. N. Witte Self-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells Stem Cells, November 1, 2007; 25(11): 2760 - 2769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lee, J. M. Basak, S. Demehri, and R. Kopan Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes Development, August 1, 2007; 134(15): 2795 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Barbaro, A. Testa, E. Di Iorio, F. Mavilio, G. Pellegrini, and M. De Luca C/EBP{delta} regulates cell cycle and self-renewal of human limbal stem cells J. Cell Biol., July 30, 2007; 177(6): 1037 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yugawa, K. Handa, M. Narisawa-Saito, S.-i. Ohno, M. Fujita, and T. Kiyono Regulation of Notch1 Gene Expression by p53 in Epithelial Cells Mol. Cell. Biol., May 15, 2007; 27(10): 3732 - 3742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lefort, A. Mandinova, P. Ostano, V. Kolev, V. Calpini, I. Kolfschoten, V. Devgan, J. Lieb, W. Raffoul, D. Hohl, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCK{alpha} kinases Genes & Dev., March 1, 2007; 21(5): 562 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Koster, D. Dai, B. Marinari, Y. Sano, A. Costanzo, M. Karin, and D. R. Roop p63 induces key target genes required for epidermal morphogenesis PNAS, February 27, 2007; 104(9): 3255 - 3260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Radoja, L. Guerrini, N. Lo Iacono, G. R. Merlo, A. Costanzo, W. C. Weinberg, G. La Mantia, V. Calabro, and M. I. Morasso Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias Development, January 1, 2007; 134(1): 13 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Blanpain, W. E. Lowry, H. A. Pasolli, and E. Fuchs Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes & Dev., November 1, 2006; 20(21): 3022 - 3035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Devgan, B.-C. Nguyen, H. Oh, and G. P. Dotto p21WAF1/Cip1 Suppresses Keratinocyte Differentiation Independently of the Cell Cycle through Transcriptional Up-regulation of the IGF-I Gene J. Biol. Chem., October 13, 2006; 281(41): 30463 - 30470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Caserta, R. Kommagani, Z. Yuan, D. J. Robbins, C. A. Mercer, and M. P. Kadakia p63 Overexpression Induces the Expression of Sonic Hedgehog Mol. Cancer Res., October 1, 2006; 4(10): 759 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Weinmaster and R. Kopan A garden of Notch-ly delights Development, September 1, 2006; 133(17): 3277 - 3282. [Abstract] [Full Text] [PDF]
|
|
