Expression of N-terminal truncated desmoglein 3 (deltaNDg3) in epidermis and its role in keratinocyte differentiation.
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 (deltaNDg3). Northern blot analysis detected a 4.6-kb transcript matching the predicted size of deltaNDg3 mRNA, and Western blot analysis with an antibody raised against the Dg3 C-terminus (H-145) detected a 31-kDa protein. Increased deltaNDg3 expression was observed in differentiating keratinocytes by RT-PCR and Western blot analysis, suggesting that deltaNDg3 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, deltaNDg3 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 deltaNDg3 led to increased migration and weakening of cell adhesion. These results suggest that deltaNDg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin.
Lee
Jung Suk
JS
Department of Dermatology, Chungnam National University, Daejeon 301-747, Korea.
Yoon
Hyun Kyung
HK
Sohn
Kyung Cheol
KC
Back
Seung Ju
SJ
Kee
Sun Ho
SH
Seo
Young Joon
YJ
Park
Jang Kyu
JK
Kim
Chang Deok
CD
Lee
Jeung Hoon
JH
D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D051184:Desmoglein 3 / Q000235:genetics* / Q000378:metabolism*; D000078404:Epidermal Cells; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D012871:Skin Diseases / Q000235:genetics / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism
D051184:Desmoglein 3; D051185:gamma Catenin