IKKα Is a p63 Transcriptional Target Involved in the Pathogenesis of Ectodermal Dysplasias
IKKα Is a p63 Transcriptional Target Involved in the Pathogenesis of Ectodermal Dysplasias
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DOI：
10.1038/jid.2008.202
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发表时间：
2009-01-01
影响因子：
6.5
通讯作者：
Costanzo, Antonio
中科院分区：
文献类型：
--
作者：
Marinari, Barbara;Ballaro, Costanza;Costanzo, Antonio
转录因子p63在表皮和上皮附属物的发育和分化中起关键作用。事实上，p63的突变与一组以皮肤、肢体和颅面缺陷为特征的外胚层发育不良有关。假设p63通过激活表皮发育过程中的特定基因来发挥其功能，从而调节表皮的分层和分化。我们已经确定I-kappaB激酶α (IKK α)作为p63的直接转录靶点，在原发性角质形成细胞终末分化的早期阶段被诱导。我们发现Delta Np63异构体是分化角质形成细胞中IKK α表达所必需的，并且外胚层发育不良患者中表达的突变p63蛋白在诱导IKK α方面表现出缺陷。此外，我们观察到强直球外胚层发育不良裂裂患者表皮中IKK α表达降低。我们的数据表明，IKK α正确表达的失败可能在外胚层发育不良的发展中起作用。
The transcription factor p63 plays a pivotal role in the development and differentiation of the epidermis and epithelial appendages. Indeed, mutations in p63 are associated with a group of ectodermal dysplasias characterized by skin, limb, and craniofacial defects. It was hypothesized that p63 exerts its functions by activating specific genes during epidermal development, which in turn regulate epidermal stratification and differentiation. We have identified I-kappaB kinase alpha (IKK alpha) as a direct transcriptional target of p63 that is induced at early phases of terminal differentiation of primary keratinocytes. We show that the Delta Np63 isoform is required for IKK alpha expression in differentiating keratinocytes and that mutant p63 proteins expressed in ectodermal dysplasia patients exhibit defects in inducing IKK alpha. Furthermore, we observed reduced IKK alpha expression in the epidermis of an ankyloblepharon ectodermal dysplasia clefting patient. Our data demonstrate that a failure to properly express IKK alpha may play a role in the development of ectodermal dysplasias.