Goethe University Frankfurt, Germany
Ivan Dikic is a leading expert in the fields of ubiquitin biology and the autophagy pathway. He is director of the Institute of Biochemistry II (IBC2, https://www.biochem2.com) at Goethe University Frankfurt, a Senior Scholar at Genentech Inc. in San Francisco (USA) and a fellow of Max Planck Society (Germany).
He received the Gottfried Wilhelm Leibniz Prize, the highest honor awarded in Germany and is an elected member the German, European and recently the American Academy of Arts and Sciences.
Ubiquitination of proteins regulates a number of key cellular processes including protein degradation, endocytosis, translation, innate immunity and DNA repair. Ubiquitin is a critical cellular signal for two major cellular quality control pathways: the proteasome degradation system and autophagy-lysosome pathway. Recently, we have shown that pathogenic Legionella pneumophila secretes enzymes that catalyze unconventional serine ubiquitination (via phosphoribose – PR) of host proteins during bacterial infection. PR-ubiquitination impairs the function of eukaryotic cells including mitophagy, DNA repair, TNF signaling and proteasomal degradation. This activity is counteracted by the action of another Legionella effector SidJ that opposes its toxicity in yeast and mammalian cells. SidJ is a glutamylase that modifies the catalytic glutamate in the mART domain of SidEs thus blocking. I will present novel data demonstrating that PR-deubiquitination is also counteracted by bacterial effectors named DUPs (DeUbiquitinases for PR-ubiquitination).
The endoplasmic reticulum (ER) is the largest intracellular endomembrane system enabling synthesis and transport of cellular components. Constant ER turnover is needed to meet different cellular requirements and autophagy plays an important role in this process. The ER is degraded via a selective autophagy pathway (called ER-phagy) and mediated by specific ER-resident proteins that interact with LC3. ER-phagy possesses the potential to remodel or rebalance the entire ER network and – given the physical and functional connection of ER to other organelles inside the cell – ER-phagy might also impact the function of other organelles as well. I will also discuss the importance of ER-phagy in neuropathies and infection diseases.
Host: Nicola Crosetto
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