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A4: Mechanisms of post‐transcriptional regulation of plakophilin 1 (PKP1) expression and its role in carcinogenesis

Supervisor: Prof. Dr. Mechthild Hatzfeld

 

Specific aim(s)/topic(s) 

(1) Post-transcriptional control of PKP1 expression via miRNAs and RNA-binding proteins (RBPs)

(2) Regulation of alternative PKP1 3’UTR processing

 

Background and significance

Plakophilin 1 (PKP1) was discovered as a component of the desmosomal plaque. It is a major constituent of desmosomes in the skin where it strengthens intercellular cohesion. However, PKP1 as well as the related plakophilins 2 (PKP2) and 3 (PKP3) are, in addition, detected in the cytoplasm and the nucleus. Their function in these compartments is still not well understood despite some recent progress in this field. PKP1 and 3 were found in stress granules, particles that are enriched in mRNAs, translation initiation factors and RNA-binding proteins (RBPs) , and stimulate mRNA translation as well as cell proliferation in non-stressed cells. Typically, intercellular cohesion correlates with contact-dependent growth inhibition, and in agreement a downregulation of desmosomal proteins including plakophilins was detected in some tumor samples. However, an upregulation of PKP1 and 3 has also been described, which led to the suggestion that the contribution of desmosomes to carcinogenesis is context-dependent although this ‘context’ has not been revealed yet.