title: The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection.
abstract: Macrophage-mediated innate immune responses play crucial roles in host defense against pathogens. Recent years have seen an explosion of host proteins that act as restriction factors blocking viral replication in infected cells. However, the essential factors restricting Mycobacterium tuberculosis (Mtb) and their regulatory roles during mycobacterial infection remain largely unknown. We previously reported that Mtb tyrosine phosphatase PtpA, a secreted effector protein required for intracellular survival of Mtb, inhibits innate immunity by co-opting the host ubiquitin system. Here, we identified a new PtpA-interacting host protein TRIM27, which is reported to possess a conserved RING domain and usually acts as an E3 ubiquitin ligase that interferes with various cellular processes. We further demonstrated that TRIM27 restricts survival of mycobacteria in macrophages by promoting innate immune responses and cell apoptosis. Interestingly, Mtb PtpA could antagonize TRIM27-promoted JNK/p38 MAPK pathway activation and cell apoptosis through competitively binding to the RING domain of TRIM27. TRIM27 probably works as a potential restriction factor for Mtb and its function is counteracted by Mtb effector proteins such as PtpA. Our study suggests a potential tuberculosis treatment via targeting of the TRIM27-PtpA interfaces.
authors.affiliation: CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Jade L L
authors.initials: JL
authors.lastname: Teng
authors.affiliation: CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Pupu
authors.initials: P
authors.lastname: Ge
authors.affiliation: CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bingxi
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong, China.
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
authors.affiliation: CAS key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
authors.forename: Cui Hua
authors.initials: CH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054829:RING Finger Domains; D014376:Tuberculosis / Q000378:metabolism / Q000382:microbiology*; D000070584:Tripartite Motif Proteins
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D048670:MAP Kinase Kinase 4; D009687:Nuclear Proteins; D017027:Protein Tyrosine Phosphatases; C414465:MptpA protein, Mycobacterium tuberculosis; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins