Modulation of the Ubiquitination Machinery by Legionella
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The bacterial pathogen Legionella pneumophila manipulates its intracellular fate by co-opting host processes. Using bacterial proteins translocated into host cells, L. pneumophila targets pathways shared by unicellular protozoa and higher eukaryotes. In eukaryotes, an important mechanism that regulates numerous cellular processes, including those designed to kill invading microorganisms, is ubiquitination. Post-translational modification of proteins with ubiquitin is a highly regulated process that either targets proteins for degradation or modifies their activity. It is emerging that L. pneumophila possesses functional mimics of eukaryotic E3 ubiquitin ligases that function with the host ubiquitination machinery to select and modify substrates for polyubiquitination. L. pneumophila proteins have been identified that ubiquitinate both host and bacterial proteins, and ubiquitination of the bacterial protein SidH results in its degradation by the host proteasome. This pathway allows L. pneumophila to temporally regulate effector function inside host cells, and facilitates optimal L. pneumophila replication by undefined mechanisms. This review will focus on our current knowledge of the proteins used by L. pneumophila to co-opt the host ubiquitination machinery, and current progress toward understanding the ubiquitin-mediated processes manipulated by L. pneumophila to facilitate intracellular survival and propagation.
KeywordsEffector Protein HECT Domain Host Pathway Host Process Dali Formation
We thank Drs Xuan Bui Thanh and Masafumi Koike for critical reading of the manuscript. Research in the Nagai laboratory was supported by Grants-in-Aid for Scientific Research (23117002, 23390105, 24659198) from Ministry of Education, Culture, Sports, Science and Technology, Japan. Andree Hubber is supported by a postdoctoral fellowship for foreign researchers awarded by the Japanese Society for the Promotion of Science (JSPS).
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