Degradation of transcription factor RFX5 during the inhibition of both constitutive and interferon gamma-inducible major histocompatibility complex class I expression in chlamydia-infected cells.
We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-gamma-inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-gamma-inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-gamma-inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.
Zhong
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Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E OW3, Canada. zhongg@uthscsa.edu
Liu
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Fan
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Fan
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Ji
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D001426:Bacterial Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex