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Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):381-8. Epub 2007 Jul 27.

A scientific journey through the 2-5A/RNase L system.

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Department of Cancer Biology, NB40 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.


The antiviral and antitumor actions of interferons are caused, in part, by a remarkable regulated RNA cleavage pathway known as the 2-5A/RNase L system. 2'-5' linked oligoadenylates (2-5A) are produced from ATP by interferon-inducible synthetases. 2-5A activates pre-existing RNase L, resulting in the cleavage of RNAs within single-stranded regions. Activation of RNase L by 2-5A leads to an antiviral response, although precisely how this happens is a subject of ongoing investigations. Recently, RNase L was identified as the hereditary prostate cancer 1 gene. That finding has led to the discovery of a novel human retrovirus, XMRV. My scientific journey through the 2-5A system recounts some of the highlights of these efforts. Knowledge gained from studies on the 2-5A system could have an impact on development of therapies for important viral pathogens and cancer.

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