Expression of N-terminal truncated desmoglein 3 (ΔNDg3) in epidermis and its role in keratinocyte differentiation

摘要

During a search for keratinocyte differentiation-related genes, we obtained a cDNA fragment from the 5'-untranslated region of a previously identified splicing variant of desmoglein 3 (Dg3). This transcript encodes a protein of 282 amino acids, which corresponds to the N-terminal truncated intracellular domain of Dg3 (ΔNDg3). Northern blot analysis detected a 4.6-kb transcript matching the predicted size of ΔNDg3 mRNA, and Western blot analysis with an antibody raised against the Dg3 C-terminus (H-145) detected a 31-kDa protein. Increased ΔNDg3 expression was observed in differentiating keratinocytes by RT-PCR and Western blot analysis, suggesting that ΔNDg3 is indeed a differentiation-related gene product. In immunohistochemical studies of normal and pathologic tissues, H-145 antibody detected the protein in the cytoplasm of suprabasal layer cells, whereas an antibody directed against the N-terminal region of Dg3 (AF1720) reacted with a membrane protein in the basal layer. In addition, ΔNDg3 transcript and protein were upregulated in psoriatic epidermis, and protein expression appeared to increase in epidermal tumors including Bowen's disease and squamous cell carcinoma. Moreover, overexpression of ΔNDg3 led to increased migration and weakening of cell adhesion. These results suggest that ΔNDg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin.