IKKα Is a p63 Transcriptional Target Involved in the Pathogenesis of Ectodermal Dysplasias
| Autor: | Maria Laura Giustizieri, Marina Papoutsaki, Dennis R. Roop, Francesca Crosti, Sergio Chimenti, Costanza Ballarò, Maranke I. Koster, Antonio Costanzo, Stefano Alemà, Francesca Moretti, Michael Karin, Barbara Marinari |
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| Jazyk: | angličtina |
| Předmět: |
Gene isoform
Keratinocytes Pathology medicine.medical_specialty Ectodermal dysplasia Transcription Genetic Dermatology Biology medicine.disease_cause Transfection Biochemistry Models Biological Gene Expression Regulation Enzymologic RNA interference Ectodermal Dysplasia Cell Line Tumor medicine Humans Protein Isoforms RNA Messenger Transcription factor Molecular Biology Regulation of gene expression Mutation Epidermis (botany) integumentary system Kinase Tumor Suppressor Proteins Cell Biology medicine.disease Cell biology I-kappa B Kinase Gene Expression Regulation Trans-Activators RNA Interference Transcription Factors |
| Zdroj: | Journal of Investigative Dermatology. (1):60-69 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2008.202 |
| Popis: | 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 (IKKalpha) as a direct transcriptional target of p63 that is induced at early phases of terminal differentiation of primary keratinocytes. We show that the DeltaNp63 isoform is required for IKKalpha expression in differentiating keratinocytes and that mutant p63 proteins expressed in ectodermal dysplasia patients exhibit defects in inducing IKKalpha. Furthermore, we observed reduced IKKalpha expression in the epidermis of an ankyloblepharon ectodermal dysplasia clefting patient. Our data demonstrate that a failure to properly express IKKalpha may play a role in the development of ectodermal dysplasias. |
| Databáze: | OpenAIRE |
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