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Status |
Public on Dec 31, 2013 |
Title |
hCAF1/CNOT7 regulates interferon signaling by targeting STAT1 |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Stringent regulation of the interferon signaling pathway is essential for maintaining the immune response to pathogens and tumors. The transcription factor STAT1 is a crucial mediator of this response. Here we show that hCAF1/CNOT7 regulates class I and II interferon 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. Consistent, 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 tumor escape.
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Overall design |
mRNAs from cells expressing the siRNA siRNA duplexes targeting hCAF1, corresponding to the coding region 941-961 (kd) (hCAF1 NCBI Reference Sequence: NM_013354.5) and one non-targeting control siRNA (mock).
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Contributor(s) |
Chapat C, Kolytcheff C, Le Romancer M, Auboeuf D, de la Grange P, Chettab K, Sentis S, Corbo L |
Citation(s) |
23386060 |
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Submission date |
Jan 08, 2013 |
Last update date |
Feb 18, 2019 |
Contact name |
Pierre de la Grange |
E-mail(s) |
pierre.delagrange@genosplice.com
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Organization name |
GenoSplice technology
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Department |
Paris Biotech Santé
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Street address |
29, rue du Faubourg Saint-Jacques
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City |
Paris |
ZIP/Postal code |
75014 |
Country |
France |
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Platforms (2) |
GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
GPL5188 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] |
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Samples (12)
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Relations |
BioProject |
PRJNA185473 |