The MP1/MAPK scaffold and compartmentalization of signaling - Regulation of MAPK and PP2A signaling complexes by PKC isotypes

During this decade, cancer is thought to become the leading cause of death in western societies, thereby overtaking human death rates of atherosclerosis and coronary heart disease. Thus this SRP is investigating a biologically and clinically significant topic. Due to its multidisciplinary nature the project areas within the SRP are synergistic, spanning from basic molecular concepts in signal transduction to clinical tumors such as epithelial tumors (prostate, mammary) and tumors of lymphatic origin. By using relevant biological systems and by exploiting "state of the art" technology, the ambitious goal of this SRP is to understand key molecular pathways that link signals leading either to programmed cell death or to cell proliferation. Too little of programmed cell death is known to enhance tumor progression, ultimately causing cancer in humans. In the first funding period, the molecular functions of selected molecules and gene products that play a role in cellular activation, e.g. as mitogenic or apoptotic signals, but also in tumorigenesis of human malignancies will be studied. The key molecules and pathways to be investigated are primarily cytotoxic anticancer drugs, hormones, IGF-binding proteins, the Bcl-2 rheostat as well as the key signaling pathways of the MAPK-cascade and of Akt/PKB. The hunt is now to understand which cells do not normally die, why and how precisely, and to find novel drugs that interfere with specific steps along the pathway(s).