Project A3: Regulation of translation by Plakophilin 1 and its function in growth control
Supervisor: Prof. Dr. Mechthild Hatzfeld
- The role of plakophilin 1 (PKP1) in translational control
- Relevance of PKP1 mediated translational regulation in tumor cell growth control
Background and significance:
Plakophilins 1-3 (PKP1-3) are essential components of the desmosomal plaque that regulate desmosome number, size and stability. These proteins belong to the armadillo superfamily which also includes b-catenin, the prototype of a multifunctional protein that regulates cell adhesion, proliferation and, when constitutively active, functions as an oncogene. Other proteins of this family such as p120 also function in cell adhesion and cell signaling. While a function in rho-signaling has been demonstrated for p120 and the related p0071, functions of PKPs not related to desmosomal adhesion remained elusive. However, especially PKP1 reveals a prominent nuclear and cytosolic localization. Moreover, several reports showed an elevated expression of PKP1 or 3 in tumor cells. This is not consistent with their function in increasing adhesion, but strongly suggests that PKPs have additional functions, presumably in growth control which may contribute to tumorigenesis.