Disease relevance of PKP3

• With the help of specific poly- and monoclonal antibodies we have localized PKP3, by immunofluorescence or immunoelectron microscopy, to desmosomes of most simple and almost all stratified epithelia and cell lines derived therefrom, with the remarkable exception of hepatocytes and hepatocellular carcinoma cells [1].
• Here we report evidence that a member of the armadillo protein family, plakophilin 3 (PKP3), is a potential molecular target for treatment of lung cancers and might also serve as a prognostic indicator [2].
• In addition, a high level of PKP3 expression was associated with poor survival as well as disease stage and node status for patients with lung adenocarcinoma, suggesting an important role of the protein in development and progression of this disease [2].
• Interestingly, patients with tumors in which PKP1 and PKP3 immunoreactivity was reduced or absent exhibited local recurrences or metastases, or both, as well as poor survival [3].

High impact information on PKP3

• To investigate its function, we searched for PKP3-interacting proteins and identified dynamin 1-like, which was also activated in NSCLC [2].
• Treatment of NSCLC cells with small interfering RNAs of PKP3 suppressed growth of the cancer cells; on the other hand, induction of exogenous expression of PKP3 conferred growth-promoting activity on COS-7 cells and enhanced their mobility in vitro [2].
• Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer [2].
• Moreover, the RNA-binding proteins codistributed after sucrose gradient centrifugation in PKP3-containing fractions corresponding to 25-35 S and 45-55 S [4].
• Moreover, the protein eIF-4E and the ribosomal protein S6 are also detected in PKP3 particles [4].

Biological context of PKP3

• Using recombinant DNA and immunological techniques, we have identified a novel desmosomal plaque protein that is closely related to plakophilins 1 and 2, both members of the "armadillo-repeat" multigene family, and have named it plakophilin 3 (PKP3) [1].
• As our data imply that up-regulation of PKP3 is a frequent and important feature of lung carcinogenesis, we suggest that targeting the PKP3 molecule might hold promise for development of a new therapeutic and diagnostic strategy for clinical management of lung cancers [2].

Anatomical context of PKP3

• Similarly, plakophilin 3 is present in the desmosomal plaques of intestinal and colonic cells but appears to be absent from the hepatocytic desmosomes [5].

Other interactions of PKP3

• We have also determined the structure of the human PKP3 gene and compared it with that of plakophilin 1 (PKP1) [1].

Analytical, diagnostic and therapeutic context of PKP3

• 1. Northern blot analysis has shown that PKP3 mRNA has a size of approximately 2.9 kb and is detectable in the total RNA of cells of stratified and single-layered epithelia [1].
• The presence of PKP 3 in adenocarcinomas was confirmed by immunoblotting [6].

References