Figures & data
Figure 1. Intracellular functions of Yersinia outer proteins (Yops). YopE, YopT, and YopO inactivate RhoGTPases, thus mainly inhibiting phagocytosis, together with YopH, which dephosphorylates components of focal adhesion complexes. YopP (YopJ in Y. pestis and Y. pseudotuberculosis) blocks NF-κB- and MAPK-signaling probably by acetylation of important signal transducers. YopM associates with PRK and RSK and regulates pro- and anti-inflammatory gene transcription via a yet unknown mechanism. The figure was generated using Servier Medical Art.
Figure 2. Overview of potential therapeutic uses of Yops. The most promising therapeutic application of YopM is the treatment of the auto-inflammatory diseases such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel diseases (IBD). Based on the molecular mechanism described before, potential areas of medical application for a recombinant, cell-penetrating YopE protein are IBD. YopT and especially its downstream target Rho-associated protein kinase ROCK are involved in several disease patterns, often within the cardiovascular field e.g., arteriosclerosis but also erectile dysfunction and traumatized neurons might be a target for a cell-penetrating YopT. A cell-penetrating effector YopO might be beneficial for the treatment of diseases associated with hyperactivated Rho-GTPases similar to YopE and YopT, but also for targeting mediators of auto-immune diseases like inflammatory bowel diseases. YopJ and its impact on signaling cascade displays potential therapeutic potential for inflammatory disorders, such as Psoriasis, RA, and IBD, but also for cancer control. RA also appears to be a promising area of application for recombinant YopH. Moreover, cancer progression also relies on signaling pathways tackled by the effector protein. The figure was produced using Servier Medical Art.
Table 1. Known functions and molecular targets of YopJ/P sorted by host cell types and stimuli. Unless stated otherwise, all listed targets are negatively regulated by YopJ/P. Targets for which direct interaction with YopJ/P was not shown in the respective references, are marked with (?).
Table 2. Known functions and molecular targets of YopH sorted by Yersinia species, host cell types and stimuli. Unless stated otherwise, all listed targets are negatively regulated by YopH. Ag = antigen, DC = dendritic cell, hum. = human, mur = murine, ROS = reactive oxygen species, TCR = T-cell receptor.