Identification and functional characterization of two new transcriptional variants of the human p63 gene.

Identification and functional characterization of two new transcriptional variants of the human p63 gene.
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DOI:
10.1093/nar/gkp674
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发表时间:
2009-10
影响因子:
14.9
通讯作者:
D'Erchia AM
D'Erchia AM
中科院分区:
生物学2区
文献类型:
--
作者:
Mangiulli M;Valletti A;Caratozzolo MF;Tullo A;Sbisà E;Pesole G;D'Erchia AM

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p63属于转录因子家族,其在显示功能结构域的显著保守性的同时,调节不同的生物学功能。其主要作用是在胚胎发生和成体组织中调节上皮定型、分化和维持程序。p63基因具有复杂的转录模式,产生两个N末端亚型(TA和ΔN),它们在C末端选择性剪接。在这里,我们报告了两个新的C-末端p63变异体的鉴定,我们命名为p63 δ和ε,从6增加到10的p63亚型的数量。所有p63变体的表达分析表明,p63替代转录表达的组织/细胞类型特异性,可能与它们不同的细胞功能有关。我们证明了新的p63变体作为ΔN异构体作为转录因子是活跃的,因为它们具有核定位并且可以调节p63靶基因的表达。此外,我们报告说,像Δ Np 63 α,Δ Np 63 δ和ε维持细胞增殖,它们的表达在角质形成细胞分化过程中减少,表明它们参与了这一过程。两者合计,我们的研究结果表明,存在新的p63蛋白的表达,应考虑在未来的研究中的作用,p63在细胞功能的调节。
p63 belongs to a family of transcription factors, which, while demonstrating striking conservation of functional domains, regulate distinct biological functions. Its principal role is in the regulation of epithelial commitment, differentiation and maintenance programs, during embryogenesis and in adult tissues. The p63 gene has a complex transcriptional pattern, producing two subclasses of N-terminal isoforms (TA and ΔN) which are alternatively spliced at the C-terminus. Here, we report the identification of two new C-terminus p63 variants, we named p63 δ and ε, that increase from 6 to 10 the number of the p63 isoforms. Expression analysis of all p63 variants demonstrates a tissue/cell-type-specific nature of p63 alternative transcript expression, probably related to their different cellular functions. We demonstrate that the new p63 variants as ΔN isoforms are active as transcription factors as they have nuclear localization and can modulate the expression of p63 target genes. Moreover, we report that, like ΔNp63α, ΔNp63δ and ε sustain cellular proliferation and that their expression decreases during keratinocyte differentiation, suggesting their involvement in this process. Taken together, our results demonstrate the existence of novel p63 proteins whose expression should be considered in future studies on the roles of p63 in the regulation of cellular functions.
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发表时间: 2006-07-01
影响因子: 14.9
作者:
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影响因子: 6.5
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发表时间: 2006-02-03
影响因子: 4.8
作者:
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