The role of protein kinases and phosphatases in the regulation of autophagy

Speaker: Prof. Joern Dengjel
Institution: University of Fribourg, Fribourg, Switzerland
Place: Jerónimo Forteza conference room, CIPF

Abstract:

Autophagy is an evolutionary conserved, vital cellular recycling pathway that is often found dysregulated in human diseases. Depending on the subtype, single proteins or entire organelles can get degraded in lysosomes, either selectively or in a less selective, bulk manner. We study the regulation of macroautophagy in which double membrane organelles, i.e. autophagosomes, are formed de novo to enwrap cytoplasm and target it for lysosomal degradation. Protein and lipid kinases and phosphatases regulate autophagy initiation as well as autophagosome maturation and fusion with lysosomes. Using protein biochemistry and mass spectrometry-based proteomics we develop in vitro and in vivo assays to study kinase-phosphatase crosstalk focusing on the serine-threonine kinase complex ULK1 and PP1 and PP2A phosphatase complexes. We could show that the regulatory PP2A subunit Striatin is a bona fide ULK1 target serving as positive feedback to promote autophagy-dependent protein turnover. Currently, we study a deep interactome of the ULK1 holo-complex to identify new protein-protein interactions that are critical for autophagy regulation.

PATROCINADO POR: 

With support from the Generalitat Valenciana, AMPER-02/2023 and CIAORG/2022/035