The desmosomal cadherin Desmoglein-3 (Dsg3) is a core adhesion component in desmosome junctions that occur with high frequency in the stratified squamous epithelial membrane lining the skin and mucous membrane. Dsg3 is identified as a major target of the circulating autoantibodies in Pemphigus Vulgaris (PV), an autoimmune blistering skin disease, and many signaling pathways have been demonstrated to be activated by PV-IgG targeting Dsg3, highlighting its role as a surface regulator in cell signaling. A recent study has revealed an unprecedented role of Dsg3 in the suppression of p53 and shows dysfunction of this pathway in PV. Furthermore, reciprocal crosstalk between p53 and yes-associated protein (YAP) downstream of Dsg3 has been observed in keratinocytes in which increased YAP expression causes suppression of p53 or vice versa. Both p53 and YAP are the crucial nuclear transcription factors involved in regulating cell fate decision, adaptation and tissue integrity in response to environmental and biological cues and are mutually exclusive in human cancer. In this review, we discuss Dsg3 signaling role in keratinocyte response to stress signals, with the highlight on our recent findings of the Dsg3/p53 pathway in the control of cell proliferation and tissue homeostasis, including the DNA integrity, beyond its function in cell-cell adhesion.
Desmoglein-3, p53, YAP, Cell signaling, DNA damage, Pemphigus