AUTHOR=Kitao Tomoe , Nagai Hiroki , Kubori Tomoko 

TITLE=Divergence of Legionella Effectors Reversing Conventional and Unconventional Ubiquitination

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00448

DOI=10.3389/fcimb.2020.00448

ISSN=2235-2988

ABSTRACT=The intracellular bacterial pathogen Legionella pneumophila employs bacteria-derived effector proteins in a variety of functions to exploit host cellular systems. The ubiquitination machinery constitutes a crucial eukaryotic system for the regulation of numerous cellular processes and is a representative target for effector-mediated bacterial manipulation. L. pneumophila transports more than 300 effector proteins into host cells through the bacterial type IV secretion system. Among these, several effector proteins have been found to function as ubiquitin ligases, including unprecedented enzymes that catalyze ubiquitination through unconventional mechanisms. Recent studies have identified many L. pneumophila effector proteins that can interfere ubiquitination. These effectors include proteins that are distantly related to the ovarian tumor protein superfamily described as deubiquitinases (DUBs), which regulate important signaling cascades in human cells. Intriguingly, L. pneumophila DUBs are not limited to enzymes that exhibit canonical DUB activity. Some L. pneumophila DUBs can catalyze the cleavage of the unconventional linkage of ubiquitin and substrates. Furthermore, novel mechanisms have been found to adversely affect the function of specific ubiquitin ligases; for instance, an effector-mediated posttranslational modification of ubiquitin ligases results in inhibition of their activity. Bacterial ubiquitin ligases and bacterial enzymes that inhibit ligase activity, including the cognate DUBs, are examples of effector/metaeffector sets due to their opposing functional relationship. In the context of L. pneumophila infection, the existence of the enzymes that reverse ubiquitination mainly relates to a fine tuning of biogenesis and remodeling of the Legionella-containing vacuole as a replicative niche. The complexity of the effector arrays reflects sophisticated strategies that bacteria have adopted to adapt its host environment and enable its survival in host cells. This review summarizes the current state of knowledge on the divergent mechanisms of the L. pneumophila effectors that can reverse ubiquitination, which is mediated by other effectors as well as by host ubiquitin machinery.