Legionella pneumophila Effector Protein LegU1 Mediates the Ubiquitination of Endoplasmic Reticulum Chaperone BiP.

The facultative intracellular pathogen Legionella pneumophila, which causes Legionnaires' disease, translocates over 300 effector proteins into the host cell. By hijacking numerous host cellular signaling pathways, these effectors promote bacterial survival and growth. One of the effector proteins, LegU1, is a F-box containing protein that binds to the host cell protein Skp1 to form a Skp1-Cullin-F-box protein (SCF) complex conferred E3 ubiquitin ligase activity. However, the role of LegU1 during L. pneumophila infection is incompletely known. Here, we demonstrate that LegU1 participates in modulation of the host BiP, an important endoplasmic reticulum chaperone that functions as both a master regulator and target protein of the unfolded protein response (UPR) process, during L. pneumophila infection. Ectopically expressed LegU1 localizes to the endoplasmic reticulum (ER) through the region from the 88th to the 136th residue. Deletion of LegU1 increases the protein level of BiP during L. pneumophila infection. We finally indicate that LegU1 interacts with and mediates the ubiquitinational degradation of BiP. Altogether, our study identifies BiP as a new substrate of LegU1 and provides new insight into how L. pneumophila modulates the host UPR pathway during infection.