Understanding the development of chronic dermatitis
31st March 2011
Mice deficient in the protein SHARPIN suffer from chronic proliferative dermatitis, with the underlying pathogenesis being only partly understood. The team around FMLS director Ivan Dikic now discovered a novel role of SHARPIN, which might explain the severe phenotypes observed in mice. The scientists showed that SHARPIN is part of the LUBAC complex and stimulates the formation of linear chains of the ubiquitin protein. These linear ubiquitin chains are attached to the NEMO protein, subsequently triggering activation of NF-κB, a transcription factor with a central role in the regulation of immune responses, cell proliferation and development. Absence of SHARPIN leads to dysregulation of this signalling pathway. In addition, the scientists also showed that SHARPIN works as an inhibitor of apoptosis via a separate signalling pathway. If SHARPIN is not functional, cell death is increased. This is a potential mechanism by which inflammatory skin lesions are formed in SHARPIN deficient mice. Link to full article and German / English press release.