Plakoglobin as a regulator of desmocollin gene expression.

Tokonzaba, Etienne; Chen, Jiangli; Cheng, Xing; Den, Zhining; Ganeshan, Radhika; Müller, Eliane Jasmine; Koch, Peter J. (2013). Plakoglobin as a regulator of desmocollin gene expression. Journal of Investigative Dermatology, 133(12), pp. 2732-2740. Nature Publishing 10.1038/jid.2013.220

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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-κB pathway components, the downstream effectors of the ectodysplasin-A (EDA)/ ectodysplasin-A receptor (EDAR)/NF-κB signaling cascade, can activate Dsc2 expression. We hypothesize that Lef-1 and EDA/EDAR/NF-κB 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Müller, Eliane Jasmine

Subjects:

600 Technology > 630 Agriculture

ISSN:

0022-202X

Publisher:

Nature Publishing

Language:

English

Submitter:

Susanne Portner

Date Deposited:

07 Aug 2014 13:45

Last Modified:

05 Dec 2022 14:30

Publisher DOI:

10.1038/jid.2013.220

PubMed ID:

23652796

BORIS DOI:

10.7892/boris.44807

URI:

https://boris.unibe.ch/id/eprint/44807

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