| First Author | Tokonzaba E | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 12 | Pages | 2732-2740 |
| PubMed ID | 23652796 | Mgi Jnum | J:202875 |
| Mgi Id | MGI:5522637 | Doi | 10.1038/jid.2013.220 |
| Citation | Tokonzaba E, et al. (2013) Plakoglobin as a regulator of desmocollin gene expression. J Invest Dermatol 133(12):2732-40 |
| abstractText | Desmosomes are cell adhesion junctions required for the normal development and maintenance of mammalian tissues and organs such as the skin, skin appendages, and the heart. The goal of this study was to investigate how desmocollins (DSCs), transmembrane components of desmosomes, are regulated at the transcriptional level. We hypothesized that differential expression of the Dsc2 and Dsc3 genes is a prerequisite for normal development of skin appendages. We demonstrate that plakoglobin (Pg) in conjunction with lymphoid enhancer-binding factor 1 (Lef-1) differentially regulates the proximal promoters of these two genes. Specifically, we found that Lef-1 acts as a switch activating Dsc2 and repressing Dsc3 in the presence of Pg. Interestingly, we also determined that NF-kappaB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-kappaB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-kappaB signaling contribute to a shift in Dsc isoform expression from Dsc3 to Dsc2 in placode keratinocytes. It is tempting to speculate that this shift is required for the invasive growth of placode keratinocytes into the dermis, a crucial step in skin appendage formation. |
