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p63是上皮分层程序启动的分子开关。

p63 is the molecular switch for initiation of an epithelial stratification program.

作者信息

Koster Maranke I, Kim Soeun, Mills Alea A, DeMayo Francesco J, Roop Dennis R

机构信息

Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Genes Dev. 2004 Jan 15;18(2):126-31. doi: 10.1101/gad.1165104. Epub 2004 Jan 16.

DOI:10.1101/gad.1165104
PMID:14729569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC324418/
Abstract

Development of stratified epithelia, such as the epidermis, requires p63 expression. The p63 gene encodes isoforms that contain (TA) or lack (DeltaN) a transactivation domain. We demonstrate that TAp63 isoforms are the first to be expressed during embryogenesis and are required for initiation of epithelial stratification. In addition, TAp63 isoforms inhibit terminal differentiation, suggesting that TAp63 isoforms must be counterbalanced by DeltaNp63 isoforms to allow cells to respond to signals required for maturation of embryonic epidermis. Our data demonstrate that p63 plays a dual role: initiating epithelial stratification during development and maintaining proliferative potential of basal keratinocytes in mature epidermis.

摘要

分层上皮组织(如表皮)的发育需要p63的表达。p63基因编码含有(TA)或缺乏(DeltaN)反式激活结构域的异构体。我们证明TAp63异构体是胚胎发育过程中首先表达的,并且是上皮分层起始所必需的。此外,TAp63异构体抑制终末分化,这表明TAp63异构体必须被DeltaNp63异构体所平衡,以使细胞能够响应胚胎表皮成熟所需的信号。我们的数据表明p63发挥双重作用:在发育过程中启动上皮分层,并维持成熟表皮中基底角质形成细胞的增殖潜能。

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p63 is the molecular switch for initiation of an epithelial stratification program.p63是上皮分层程序启动的分子开关。
Genes Dev. 2004 Jan 15;18(2):126-31. doi: 10.1101/gad.1165104. Epub 2004 Jan 16.
2
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3
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本文引用的文献

1
deltaNp63alpha functions as both a positive and a negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes.δNp63α作为一种正负转录调节因子发挥作用,并阻断小鼠角质形成细胞的体外分化。
Oncogene. 2003 Jun 5;22(23):3635-44. doi: 10.1038/sj.onc.1206536.
2
DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development.DeltaNp63α和TAp63α在癌症和发育过程中调控具有不同生物学功能的基因转录。
Cancer Res. 2003 May 15;63(10):2351-7.
3
The Delta Np63 alpha phosphoprotein binds the p21 and 14-3-3 sigma promoters in vivo and has transcriptional repressor activity that is reduced by Hay-Wells syndrome-derived mutations.Delta Np63α磷酸化蛋白在体内与p21和14-3-3σ启动子结合,并具有转录抑制活性,该活性会因海-韦综合征衍生的突变而降低。
Mol Cell Biol. 2003 Apr;23(7):2264-76. doi: 10.1128/MCB.23.7.2264-2276.2003.
4
Notch1 functions as a tumor suppressor in mouse skin.Notch1在小鼠皮肤中作为一种肿瘤抑制因子发挥作用。
Nat Genet. 2003 Mar;33(3):416-21. doi: 10.1038/ng1099. Epub 2003 Feb 18.
5
Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains.p63亚型的复杂转录效应:新型激活和抑制结构域的鉴定
Mol Cell Biol. 2002 Dec;22(24):8659-68. doi: 10.1128/MCB.22.24.8659-8668.2002.
6
Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma.Jagged-1介导的Notch信号激活通过NF-κB和PPARγ诱导人角质形成细胞完全成熟。
Cell Death Differ. 2002 Aug;9(8):842-55. doi: 10.1038/sj.cdd.4401036.
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K14-GLp65 transactivator induces transgene expression in embryonic epidermis.K14-GLp65反式激活因子诱导胚胎表皮中的转基因表达。
Genesis. 2002 Feb;32(2):189-90. doi: 10.1002/gene.10063.
8
Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation.Notch信号通路是角质形成细胞生长停滞并进入分化状态的直接决定因素。
EMBO J. 2001 Jul 2;20(13):3427-36. doi: 10.1093/emboj/20.13.3427.
9
p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes.p63α和ΔNp63α可诱导细胞周期停滞和凋亡,并对p53靶基因进行差异调节。
Oncogene. 2001 May 31;20(25):3193-205. doi: 10.1038/sj.onc.1204427.
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Phenotypic consequences of lung-specific inducible expression of FGF-3.FGF-3在肺特异性诱导表达的表型后果。
Proc Natl Acad Sci U S A. 2001 May 8;98(10):5898-903. doi: 10.1073/pnas.101116598. Epub 2001 May 1.