Ubiquitylation is a widely used post-translational protein modification that regulates many biological processes, including immune responses. The role of ubiquitin in immune regulation was originally uncovered through studies of antigen presentation and the nuclear factor-κB family of transcription factors, which orchestrate host defence against microorganisms. Recent studies have revealed crucial roles of ubiquitylation in many aspects of the immune system, including innate and adaptive immunity and antimicrobial autophagy. In addition, mounting evidence indicates that microbial pathogens exploit the ubiquitin pathway to evade the host immune system. Here, we review recent advances on the role of ubiquitylation in host defence and pathogen evasion.
"signaling is extensively modulated by ubiquitin at various points (Belgnaoui et al., 2012; Jiang et al., 2012; Maelfait and Beyaert, 2012; Nakhaei et al., 2009b; Zeng et al., 2010; Zeng et al., 2009; Zhong et al., 2010). Notably, the ubiquitin ligase RNF5 (RMA1) catalyzes K48-linked polyubiquitination of STING, promoting the proteasome-mediated degradation of STING (Zhong et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: Toll-like receptors (TLRs) play crucial roles in the innate immune system by recognizing pathogen-associated molecular patterns derived from various microbes. TLRs signal through the recruitment of specific adaptor molecules, leading to activation of the transcription factors NF-κB and IRFs, which dictate the outcome of innate immune responses. During the past decade, the precise mechanisms underlying TLR signaling have been clarified by various approaches involving genetic, biochemical, structural, cell biological, and bioinformatics studies. TLR signaling appears to be divergent and to play important roles in many aspects of the innate immune responses to given pathogens. In this review, we describe recent progress in our understanding of TLR signaling regulation and its contributions to host defense.
Frontiers in Immunology 09/2014; 5:461. DOI:10.3389/fimmu.2014.00461
"Modifying a protein with ubiquitin can result in a variety of outcomes other than degradation. These include activation of signaling proteins, regulation of protein-protein interactions, and relocalization of proteins within a cell (Jiang and Chen, 2012). Herein, we focus on the degradation of ubiquitylated proteins. "
[Show abstract][Hide abstract] ABSTRACT: Pathogens use various mechanisms to manipulate host processes to promote infection. Decades of research on pathogens have revealed not only the molecular mechanisms that these microbes use to replicate and survive within host cells, but also seminal information on how host signaling machinery regulates cellular processes. Among these discoveries are mechanisms involving posttranslational modifications that alter the activity, localization, or interactions of the modified protein. Herein, we examine how pathogens have contributed to our basic understanding of three posttranslational modifications: phosphorylation, NMPylation, and ubiquitylation. Over the years, technologies, techniques and research tools have developed side by side with the study of pathogens, facilitating the discovery of protein modifications and furthering our understanding of how they contribute to both infection and cellular functions.
Elsa Jacouton, Núria Mach, Julie Cadiou, Nicolas Lapaque, Karine Clément, Joël Doré, Johan E T van Hylckama Vlieg, Tamara Smokvina, Hervé M Blottière
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.