1. hCAF1/CNOT7 regulates interferon signalling by targeting STAT1
- Author
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Chloé Kolytcheff, Clément Chapat, Muriel Le Romancer, Kamel Chettab, Didier Auboeuf, Pierre de la Grange, Laura Corbo, and Stéphanie Sentis
- Subjects
Chromatin Immunoprecipitation ,Cytoplasm ,Blotting, Western ,Fluorescent Antibody Technique ,Apoptosis ,Breast Neoplasms ,Biology ,Real-Time Polymerase Chain Reaction ,Virus Replication ,Article ,General Biochemistry, Genetics and Molecular Biology ,Immune system ,Interferon ,Biomarkers, Tumor ,medicine ,Humans ,Immunoprecipitation ,Gene silencing ,RNA, Messenger ,STAT1 ,Phosphorylation ,RNA, Small Interfering ,Promoter Regions, Genetic ,Molecular Biology ,Transcription factor ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Innate immune system ,General Immunology and Microbiology ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,General Neuroscience ,Molecular biology ,Immunity, Innate ,Cell biology ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,MicroRNAs ,STAT1 Transcription Factor ,Exoribonucleases ,biology.protein ,Female ,Interferons ,Signal transduction ,Signal Transduction ,Transcription Factors ,medicine.drug - Abstract
Stringent regulation of the interferon (IFN) signalling pathway is essential for maintaining the immune response to pathogens and tumours. The transcription factor STAT1 is a crucial mediator of this response. Here, we show that hCAF1/CNOT7 regulates class I and II IFN pathways at different crucial steps. In resting cells, hCAF1 can control STAT1 trafficking by interacting with the latent form of STAT1 in the cytoplasm. IFN treatment induces STAT1 release, suggesting that hCAF1 may shield cytoplasmic STAT1 from undesirable stimulation. Consistently, hCAF1 silencing enhances STAT1 basal promoter occupancy associated with increased expression of a subset of STAT1-regulated genes. Consequently, hCAF1 knockdown cells exhibit an increased protection against viral infection and reduced viral replication. Furthermore, hCAF1 participates in the extinction of the IFN signal, through its deadenylase activity, by speeding up the degradation of some STAT1-regulated mRNAs. Since abnormal and unbalanced JAK/STAT activation is associated with immune disorders and cancer, hCAF1 could play a major role in innate immunity and oncogenesis, contributing to tumour escape.
- Published
- 2013