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  • The EMBO Journal (2006) 25, 3298 - 3309
  • doi:10.1038/sj.emboj.7601224

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

Lina Williamson1, Natalia A Raess1, Reto Caldelari1, Anthony Zakher1, Alain de Bruin1,a, Horst Posthaus1, Reinhard Bolli2, Thomas Hunziker3, Maja M Suter1 and Eliane J Müller1

  1. Molecular Dermatology, Institute Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  2. Zentral Labor Bern-Behring, Bern, Switzerland
  3. Department Dermatology, Medical Faculty, University of Bern, Bern, Switzerland

Correspondence to:

Eliane J Müller, Molecular Dermatology, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Postfach, Länggass-Str. 122, Bern 3001, Switzerland. Tel.: +41 31 631 24 03 or 631 23 98; Fax: +41 31 631 26 35; E-mail: eliane.mueller@itpa.unibe.ch

aPresent address: Department of Pathobiology, Faculty of Veterinary Medicine, University of Utrecht, Yalelaan 1, 3584 CL Utrecht, The Netherlands

Received 27 January 2006; Accepted 9 June 2006

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.

  • Keywords:

    • beta-catenin,
    • desmosomes,
    • epidermis,
    • stem cells,
    • plakoglobin