The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation.
Snail, a transcriptional repressor of E-cadherin expression, is involved in epithelial-mesenchymal transitions during development. We demonstrate that Snail activity is not restricted to E-cadherin downregulation. Expression of tight junction proteins, including claudin-1, occludin and ZO-1, was downregulated in MDCK cells exogenously expressing Snail protein. Although occludin mRNA levels were downregulated by Snail expression, the transcription of claudin-1 and ZO-1 were unaffected. Reporter assays using the claudin-1 promoter region revealed that promoter activity was not affected by Snail overexpression. Decreased synthesis of claudin-1 protein was observed, however, suggesting that Snail may act in translation initiation. Snail expression also altered the splicing pattern of p120. The levels of mRNA encoding the epithelial variant decreased, while the fibroblastic mRNA form increased. Although ectopic E-cadherin expression resulted in a downregulation of Snail-induced fibronectin expression, fibroblastic morphology was affected only minimally; the expression of tight junctional proteins remained at low levels. These results indicate that Snail is involved in both the direct transcriptional repression of genes, such as E-cadherin and occludin, and post-transcriptional events, including downregulation of claudin-1. These data support the idea that Snail is a transcription factor possessing pleiotropic activities.
Ohkubo
Tadashi
T
Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Ozawa
Masayuki
M
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D062445:Claudin-1; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000502:physiology; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071250:Snail Family Transcription Factors; D019108:Tight Junctions / Q000737:chemistry* / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin
C568108:CLDN1 protein, human; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D000071250:Snail Family Transcription Factors; C569042:TJP1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D062826:Zonula Occludens-1 Protein; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin