Analysis of isoform specific functions of atypical PKCɩ and PKCζ
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AbstractWe investigated two proteins. PKC iota and zeta, that are involved in cancer development and metastasis of tumors. I was able to show that both proteins underly different regulation regarding their nuclear import in cells. These differences are strong indicators for specific functions of each of the two proteins and stands in contrast to the former believe that both proteins are similar in their roles. Since both proteins are therapeutic targets in cancer therapy these findings might have an influence on the future of cancer therapy. The protein kinase C (PKC) iota and lambda belong to a large group (family) of protein kinases and are involved in important cellular processes such as cell growth, orientation and movement. Their role as protein kinases is to convert incoming signals into a cellular response. Their function is highly regulated through interacting proteins that either stop the protein from functioning or navigate the protein to a specific location within the cell. Cancer cells often produce much higher amounts of these proteins than usual. This ‘overexpression’ leads to proteins that act “out-of-control” and thereby might cause or support the development of cancer. In this thesis we show for the first time evidences that both proteins have different roles in the early development of mouse embryos and that their import into the nucleus of polarized cells is regulated in different ways. These data show that the common perception of protein kinase C iota and zeta as proteins with identical functions needs to be reconsidered and it is more likely, that they both proteins share some functions while having specific functions depending on the cellular context.
List of papers
Paper I: Functional comparison of protein domains within aPKCs involved in nucleocytoplasmic shuttling. Sebastian Seidl, Ursula B. Braun and Michael Leitges. May 15, 2012 Biology Open 1, 436-445. doi: 10.1242/bio.2012505
Paper II: Manuscript (under review). Phenotypical analysis of atypical PKCs in vivo function display a compensatory system at embryonic stage 7.5 p.c. Sebastian Seidl, Ursula Braun, Norbert Roos, Shaohua Li, Timo H.-W. Lüdtke, Andreas Kispert and Michael Leitges. Published in: Plos One, 2013, Vol.8(5) doi: 10.1371/journal.pone.0062756