2018
DOI: 10.1128/iai.00845-17
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Ehrlichia chaffeensis TRP120 Effector Targets and Recruits Host Polycomb Group Proteins for Degradation To Promote Intracellular Infection

Abstract: has a group of well-characterized type I secreted tandem repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate various cellular processes, reprogram host gene transcription as nucleomodulins, function as ubiquitin ligases, and directly activate conserved host cell signaling pathways to promote infection. One TRP-interacting host target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb group (PcG) protein family and a component of the polycomb repressive compl… Show more

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Cited by 26 publications
(35 citation statements)
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“…Recent results support a model in which, during E. chaffeensis infection, TRP120 relocalizes PCGF isoforms from the nucleus to the ehrlichial vacuole and induces their degradation [53] ( Figure 1C). This coincides with a decrease in the level of the PRC1-mediated epigenetic mark H2AK119Ub (histone H2A ubiquitinated at lysine 119) and in the transcriptional activation of PRC1 target genes, such as homeobox protein (HOX) encoding genes [53]. Knockdown of PCGF5 by small interfering RNAs (siRNAs) results in a significant increase in E. chaffeensis infection.…”
Section: Ankyrin Repeat-and Tandem Repeat-containing Nucleomodulins: supporting
confidence: 77%
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“…Recent results support a model in which, during E. chaffeensis infection, TRP120 relocalizes PCGF isoforms from the nucleus to the ehrlichial vacuole and induces their degradation [53] ( Figure 1C). This coincides with a decrease in the level of the PRC1-mediated epigenetic mark H2AK119Ub (histone H2A ubiquitinated at lysine 119) and in the transcriptional activation of PRC1 target genes, such as homeobox protein (HOX) encoding genes [53]. Knockdown of PCGF5 by small interfering RNAs (siRNAs) results in a significant increase in E. chaffeensis infection.…”
Section: Ankyrin Repeat-and Tandem Repeat-containing Nucleomodulins: supporting
confidence: 77%
“…Furthermore, a HECT E3 (Homologous to E6AP C-terminal ubiquitin ligase) domain is present in the C-terminal region of TRP120 and targets PCGF5 for poly-ubiquitination [52]. Recent results support a model in which, during E. chaffeensis infection, TRP120 relocalizes PCGF isoforms from the nucleus to the ehrlichial vacuole and induces their degradation [53] ( Figure 1C). This coincides with a decrease in the level of the PRC1-mediated epigenetic mark H2AK119Ub (histone H2A ubiquitinated at lysine 119) and in the transcriptional activation of PRC1 target genes, such as homeobox protein (HOX) encoding genes [53].…”
Section: Ankyrin Repeat-and Tandem Repeat-containing Nucleomodulins: mentioning
confidence: 57%
“…Recent investigations of E. chaffeensis pathobiology have revealed how TRP effectors exploit host signaling and post translational pathways and other cellular processes in order to evade host innate immune mechanisms and establish intracellular infection [6,9,[42][43][44]. Specifically, E. chaffeensis has evolved mechanisms to avoid recognition by innate immune receptors and Lysates were treated with NEM (N-ethylmaleimide, equal mass amount to whole cell lysates used) and bortezomib (10ng/ml, 10 h) to prevent deubiquitination and proteasome degradation.…”
Section: Discussionmentioning
confidence: 99%
“…Notably, a TRP120 HECT ligase substrate (PCGF5) has been identified [10]. The interaction between TRP120 and PCGF5 has been shown to occur in the nucleus during early infection (24 h) and with cytoplasmic morulae during late infection (72 h) [6]; however, TRP120 appears to interact with FBW7 in the nucleus throughout the course of infection resulting in Ub-mediated degradation of FBW7.…”
Section: Plos Pathogensmentioning
confidence: 99%
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