Background: Androgen receptor (AR) is the principle therapeutic target in prostate cancer. Result: We have established that Usp12 deubiquitinates and stabilizes the AR resulting in increased transcriptional and proproliferative activity. Conclusion:We have identified Usp12 to be a novel positive regulator of AR. Significance: Usp12 presents a therapeutic target upstream of AR that could enable bypassing the limitations of therapeutics aimed specifically at AR.

Enteropathogenic Escherichia coli (EPEC) are considered to be extracellular pathogens, inducing attaching and effacing lesions following their attachment to the surface of eukaryotic cells; however, in vitro and in vivo invasion by EPEC has been reported in several studies. A cloned 4.6 kb fragment of EPEC plasmid pLV501 has been shown to facilitate invasion of E. coli K-12, and here we further investigate the nature of this process. Two of the three complete open reading frames contained within the plasmid fragment have been cloned to E. coli, and in HEp-2 adherence assays both tniA2 and pecM were shown to be expressed during the first 3 h of infection from a plac promoter. Escherichia coli transformants carrying pecM alone or in combination with tniA2 were able to both survive intracellularly and escape eukaryotic cells to re-establish themselves within the medium, whereas those bacterial cells carrying tniA2 alone could not be isolated from within HEp-2 cells after 24 h of infection, but were present in the previously sterile medium surrounding the cells. Bacteria carrying pecM and tniA2 adhered to HEp-2 cells with sites of adhesion characterized by underlying actin polymerization. The invasive potential conferred by these genes may give EPEC strains a survival advantage during prolonged infection.