p63 Overexpression Induces the Expression of Sonic Hedgehog
p63 and p73 are members of the p53 protein family and have been shown to play an important role in cell death, development, and tumorigenesis. In particular, p63 has been shown to be involved in the maintenance of epidermal stem cells and in the stratification of the epidermis. Sonic Hedgehog (Shh)...
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Published in | Molecular cancer research Vol. 4; no. 10; pp. 759 - 768 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Association for Cancer Research
01.10.2006
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Subjects | |
Online Access | Get full text |
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Summary: | p63 and p73 are members of the p53 protein family and have been shown to play an important role in cell death, development,
and tumorigenesis. In particular, p63 has been shown to be involved in the maintenance of epidermal stem cells and in the
stratification of the epidermis. Sonic Hedgehog (Shh) is a morphogen that has also been implicated to play a role in epithelial
stem cell proliferation and in the development of organs. Recently, Shh has also been shown to play an important role in the
progression of a variety of cancers. In this report, we show that p63 and p73 but not p53 overexpression induces Shh expression.
In particular, p63γ and p63β (both TA and ΔN isoforms) and TAp73β isoform induce Shh. Expression of Shh was found to be significantly
reduced in mouse embryo fibroblasts obtained from p63−/− mice. The naturally occurring p63 mutant TAp63γ(R279H) and the tumor
suppressor protein p14 ARF inhibited the TAp63γ-mediated transactivation of Shh. The region −228 to −102 bp of Shh promoter was found to be responsive
to TAp63γ-induced transactivation and TAp63γ binds to regions within the Shh promoter in vivo . The results presented in this study implicate p63 in the regulation of the Shh signaling pathway. (Mol Cancer Res 2006;4(10):759–68) |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1541-7786 1557-3125 |
DOI: | 10.1158/1541-7786.MCR-05-0149 |