| Abstract
| - Recently, the interferon (IFN) antiviral pathways and prostate cancer genetics and havesurprisingly converged on a single-strand specific, regulated endoribonuclease. Genetics studies from severallaboratories in the U.S., Finland, and Israel, support the recent identification of the RNase L gene, RNASEL,as a strong candidate for the long sought after hereditary prostate cancer 1 (HPC1) allele. Results fromthese studies suggest that mutations in RNASEL predispose men to an increased incidence of prostatecancer, which in some cases reflect more aggressive disease and/or decreased age of onset comparedwith non-RNASEL linked cases. RNase L is a uniquely regulated endoribonuclease that requires5‘-triphosphorylated, 2‘,5‘-linked oligoadenylates (2-5A) for its activity. The presence of both germlinemutations in RNASEL segregating with disease within HPC-affected families and loss of heterozygosity(LOH) in tumor tissues suggest a novel role for the regulated endoribonuclease in the pathogenesis ofprostate cancer. The association of mutations in RNASEL with prostate cancer cases further suggests arelationship between innate immunity and tumor suppression. It is proposed here that RNase L functionsin counteracting prostate cancer by virtue of its ability to degrade RNA, thus initiating a cellular stressresponse that leads to apoptosis. This monograph reviews the biochemistry and genetics of RNase L asit relates to the pathobiology of prostate cancer and considers implications for future screening and therapyof this disease.
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