Premium
A dominant mutation etiologic for human tricho‐dento‐osseous syndrome impairs the ability of DLX3 to downregulate ΔNp63α
Author(s) -
Di Costanzo Antonella,
Festa Luisa,
Roscigno Giuseppina,
Vivo Maria,
Pollice Alessandra,
Morasso Maria,
La Mantia Girolama,
Calabrò Viola
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22553
Subject(s) - biology , homeobox , transcription factor , mutant , ectodermal dysplasia , genetics , regulation of gene expression , gene , downregulation and upregulation , locus (genetics) , microbiology and biotechnology
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 ΔNp63α, 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 ΔNp63α 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, ΔNp63α 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. © 2010 Wiley‐Liss, Inc.