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Composition and Dynamics of Macromolecular Complexes in Quality Control and Signaling

Research Area B

Integration, amplification and distribution of external and internal signals regulate cellular processes through interaction of many different macromolecular complexes. The localisation and composition of signaling complexes are dynamically regulated by post-translational modifications exerting quality control at the levels of individual molecules, organelles and even cells. In CEF-II, we will study structure and function of key complexes that are involved in three important steps, namely in dedicated quality control processes, in intracellular signal transduction and in transcription. The role of phosphorylation and ubiquitylation in cellular quality control pathways is well established, but several novel functions in organellar and cellular quality mechanisms have been identified in CEF-I. Our future research is dedicated to understand the role of ubiquitylation and other ubiquitin-like modifications as dynamic molecular switches between cell death and survival as well as autophagic removal of large protein aggregates and misfunctional organelles. We have discovered a general mechanism how phosphorylation of cargo-selective receptors can control autophagic clearance of different cargoes. We will thoroughly investigate the mechanisms of selective autophagy of protein aggregates and pathogens in this area (and mitochondria and ribosomes in research areas A and C, respectively). At the nuclear level, the composition and dynamics of transcriptional complexes and chromatin remodeling factors are essential for cellular functions. How these dynamic signals regulate oligomerization and activity of TAp63, a quality control factor of the female germ line, and the assembly of large leukemia-related transcriptional complexes and their role in physiological and pathophysiological conditions will be determined in CEF-II. 

 

Impact:

• Quantitative parameters of macromolecular interactions in cells
• Spatio-temporal regulation of signaling networks and quality control mechanisms
• Functional relevance in higher organisms