期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 13, 页码 E2950-E2959出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1720431115
关键词
type I interferon; IFN-stimulated genes; cyclin-dependent kinases; CDK inhibitors; translational regulation
资金
- NIH [R01 CA030488]
Recognition of nucleic acids results in the production of type I IFNs, which activate the JAK/STAT pathway and promote the expression of IFN-stimulated genes. In a search for modulators of this pathway, we discovered an unexpected requirement for cyclin-dependent kinases (CDK) in the production of type I IFN following nucleic acid sensing and virus infection. Inhibition of CDK activity or knockdown of CDK levels leads to a striking block in STAT activation and IFN-stimulated gene expression. CDKs are not required for the initial nucleic acid sensing leading to IFN-beta mRNA induction, nor for the response to exogenous IFN-alpha/beta, but are critical for IFN-beta release into culture supernatants, suggesting a posttranscriptional role for CDKs in type I IFN production. In the absence of CDK activity, we demonstrate a translational block specific for IFN-beta, in which IFN-beta mRNA is removed from the actively translating polysomes, while the distribution of other cellular mRNAs or global translation rates are unaffected. Our findings reveal a critical role for CDKs in the translation of IFN-beta.
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