ChlaDub1 of Chlamydia trachomatis suppresses NF-kappaB activation and inhibits IkappaBalpha ubiquitination and degradation.
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes various human diseases, including blindness caused by ocular infection and sexually transmitted diseases resulting from urogenital infection. After infecting host cells, Chlamydiae avoid alarming the host's immune system. Among the immune evasion mechanisms, Chlamydiae can inhibit NF-kappaB activation, a crucial pathway for host inflammatory responses. In this study, we show that ChlaDub1, a deubiquitinating and deNeddylating protease from C. trachomatis, is expressed in infected cells. In transfection experiments, ChlaDub1 suppresses NF-kappaB activation induced by several pro-inflammatory stimuli and binds the NF-kappaB inhibitory subunit IkappaBalpha, impairing its ubiquitination and degradation. Thus, we provide further insight into the mechanism by which C. trachomatis may evade the host inflammatory response by demonstrating that ChlaDub1, a protease produced by this microorganism, is capable of inhibiting IkappaBalpha degradation and blocking NF-kappaB activation.
Le Negrate
Gaëlle
G
Program on Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Krieg
Andreas
A
Faustin
Benjamin
B
Loeffler
Markus
M
Godzik
Adam
A
Krajewski
Stan
S
Reed
John C
JC
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000201:enzymology*; D015536:Down-Regulation; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014162:Transfection; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
D001426:Bacterial Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D047992:TNF Receptor-Associated Factor 2; D048029:TNF Receptor-Associated Factor 6; D000072000:NF-KappaB Inhibitor alpha; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases