A Dominant Mutation Etiologic for Human Tricho-Dento-Osseous Syndrome Impairs the Ability of DLX3 to Downregulate Delta Np63 alpha

作者：Di Costanzo Antonella; Festa Luisa; Roscigno Giuseppina; Vivo Maria; Pollice Alessandra; Morasso Maria; La Mantia Girolama; Calabro Viola^*

来源：Journal of Cellular Physiology, 2011, 226(8): 2189-2197.

DOI：10.1002/jcp.22553

The homeodomain transcription factors play crucial roles in many developmental processes ranging from organization of the body plan to differentiation of individual tissues. The homeodomain protein Distal-less-3 (DLX3) has an essential role in epidermal stratification and development of ectodermal appendages, placenta and bones. A four-nucleotide deletion in the human DLX3 gene is etiologic for the human hereditary tricho-dento-osseous (TDO) ectodermal dysplasia, a dominant syndrome characterized by abnormalities in hair, nails, teeth, and bones. We have previously demonstrated that DLX3 gene expression induces degradation of Delta Np63 alpha, a specific product of the TP63 gene, a master regulator of multi-layered epithelia. Here we show that the DLX3(TDO) mutant protein is unable to promote Delta Np63 alpha protein degradation and impairs the expression of cell cycle regulatory proteins and skin differentiation markers. However, we found that in cell expressing equal amounts of mutant and wild-type DLX3, Delta Np63 alpha protein level is efficiently regulated implying that genetic heterozygosity at the DLX3 locus protects TDO patients from developing severe p63-associated skin defects. J. Cell. Physiol. 226: 2189-2197, 2011.

• 出版日期2011-8