Disease relevance of OAS3

• Biochemical analyses using recombinant proteins produced in Escherichia coli showed that all the novel mouse 2-5OAS molecules have double-stranded RNA (dsRNA) binding ability, but they do not have 2-5OAS activity except for the OAS2 and OAS3 mouse homologs [1].
• Activation of the noncanonical NF-kappaB signaling pathway involved in the proteolytic processing of NF-kappaB p100 to p52 is tightly regulated, and overproduction of p52 leads to lymphocyte hyperplasia and transformation [2].
• These results show that increased p100/p52 disrupts normal ductal development and provides insight into the mechanism by which this may contribute to human breast cancer [3].

High impact information on OAS3

• Our studies demonstrate a different mechanism of p100 processing and also present evidence showing that the proteasome modulates the action of transcription factors at promoter regions through endoproteolysis [4].
• Stat3 activation of NF-{kappa}B p100 processing involves CBP/p300-mediated acetylation [2].
• After multiple pregnancies the p100 transgenics exhibited a ductal thickening accompanied by small hyperplastic foci [3].
• In tumors from mice expressing the polyoma middle T oncoprotein (PyVT) in the mammary gland, increased levels of p100/p52 were present at the time of tumor development [3].
• Indeed, further in vitro experiments established that s-rIkappaB DC undergo efficient maturation upon prolonged contact with activated T cells via the alternative pathway of NF-kappaB activation triggered at least partly by lymphotoxin beta receptor ligation and involving processing of p100/RelB complexes [5].

Biological context of OAS3

• The promoter region of the p100 gene is composed of multiple features conferring direct inducibility not only by IFNs but also by TNF and all-trans retinoic acid [6].
• An OAS3 gene was not found in either the cattle or the pig genome [7].
• Additionally, induction of p100 phosphorylation can be blocked by a protein synthesis inhibitor, suggesting the requirement of de novo protein synthesis [8].
• The pattern reversal visual evoked potentials elicited to 50' checks with three reversals per second viewed with both eyes were analyzed for n80-p100 amplitude, p100 latency, and breadth of waveform [9].

Associations of OAS3 with chemical compounds

• Mutation of either serine 866 or serine 870 abolishes the beta-TrCP recruitment and ubiquitination of p100 [8].

Other interactions of OAS3

• In mice, however, OAS genes corresponding to human OAS2 and OAS3 have not been identified [1].
• In contrast, the induction of the p100 promoter by dsRNA is indirect and requires IFN type I production [6].

Analytical, diagnostic and therapeutic context of OAS3

• Here we describe the molecular cloning and characterization of p100 [10].

References