Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin

Williamson, Lina; Raess, Natalia A; Caldelari, Reto; Zakher, Anthony; de Bruin, Alain; Posthaus, Horst; Bolli, Reinhard; Hunziker, Thomas; Suter, Maja M; Müller, Eliane J (2006). Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin. EMBO journal, 25(14), pp. 3298-309. London: Nature Publishing Group 10.1038/sj.emboj.7601224

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The autoimmune disease pemphigus vulgaris (PV) manifests as loss of keratinocyte cohesion triggered by autoantibody binding to desmoglein (Dsg)3, an intercellular adhesion molecule of mucous membranes, epidermis, and epidermal stem cells. Here we describe a so far unknown signaling cascade activated by PV antibodies. It extends from a transient enhanced turn over of cell surface-exposed, nonkeratin-anchored Dsg3 and associated plakoglobin (PG), through to depletion of nuclear PG, and as one of the consequences, abrogation of PG-mediated c-Myc suppression. In PV patients (6/6), this results in pathogenic c-Myc overexpression in all targeted tissues, including the stem cell compartments. In summary, these results show that PV antibodies act via PG to abolish the c-Myc suppression required for both maintenance of epidermal stem cells in their niche and controlled differentiation along the epidermal lineage. Besides a completely novel insight into PV pathogenesis, these data identify PG as a potent modulator of epithelial homeostasis via its role as a key suppressor of c-Myc.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Research Foci > DermFocus 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology 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:	Williamson Ramirez, Lina, Raess, Natalia, Zakher, Anthony, Posthaus, Horst, Hunziker, Thomas, Suter, Maja, Müller, Eliane Jasmine
Subjects:	600 Technology > 630 Agriculture
ISSN:	0261-4189
Publisher:	Nature Publishing Group
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1038/sj.emboj.7601224
PubMed ID:	16871158
Web of Science ID:	000239625900006
URI:	https://boris.unibe.ch/id/eprint/18690 (FactScience: 898)