PLoS Pathogens
Public Library of Science
Ehrlichia chaffeensis TRP120-mediated ubiquitination and proteasomal degradation of tumor suppressor FBW7 increases oncoprotein stability and promotes infection
Volume: 16, Issue: 4
DOI 10.1371/journal.ppat.1008541

E. chaffeensis is an obligately intracellular bacterium that replicates in mononuclear phagocytes by secreting effectors that manipulate host cell processes and exploit evolutionarily conserved pathways. This investigation reveals the complex and expanding role of the E. chaffeensis TRP120 moonlighting effector as a ubiquitin (Ub) ligase targeting host nuclear proteins. Herein, we demonstrate that E. chaffeensis TRP120 HECT Ub ligase targets the nuclear tumor suppressor Skp1-cullin-1-FBOX E3 ubiquitin (Ub) ligase complex substrate recognition subunit, F-BOX and WD domain repeating-containing 7 (FBW7) for degradation. FBW7 is a central regulator of broadly acting host cell oncoproteins involved in cell proliferation and survival. The reduction in FBW7 through TRP120-mediated ubiquitination increases cellular oncoprotein levels and promotes E. chaffeensis infection. This study illuminates novel bacterial effector-host interactions, the importance and interplay of both host and bacterial Ub ligases and the Ub-proteasome system for infection, and mechanisms whereby evolutionarily conserved signaling pathways are hijacked by obligately intracellular pathogens.<i>Ehrlichia chaffeensis</i> TRP120-mediated ubiquitination and proteasomal degradation of tumor suppressor FBW7 increases oncoprotein stability and promotes infection&author=Jennifer Y. Wang,Bing Zhu,LaNisha L. Patterson,Madison R. Rogan,Clayton E. Kibler,Jere W. McBride,Daniel E. Voth,&keyword=&subject=Research Article,Biology and Life Sciences,Biochemistry,Enzymology,Enzymes,Ligases,Biology and Life Sciences,Biochemistry,Proteins,Enzymes,Ligases,Biology and Life Sciences,Biochemistry,Proteins,Post-Translational Modification,Ubiquitination,Biology and Life Sciences,Cell Biology,Signal Transduction,Cell Signaling,Notch Signaling,Biology and Life Sciences,Microbiology,Virology,Viral Transmission and Infection,Host Cells,Biology and Life Sciences,Cell Biology,Cell Processes,Cell Death,Apoptosis,Biology and life sciences,Genetics,Gene expression,Gene regulation,Small interfering RNAs,Biology and life sciences,Biochemistry,Nucleic acids,RNA,Non-coding RNA,Small interfering RNAs,Medicine and Health Sciences,Pathology and Laboratory Medicine,Pathogenesis,Host-Pathogen Interactions,Research and Analysis Methods,Microscopy,Light Microscopy,Confocal Microscopy,