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To identify novel oncogenic E3 ubiquitin ligases as anti cancer targets, we screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the SRB assay in the MDA-MB-231 breast cancer cell line.RNF126 and BCA2 were identified and validated as candidates from this screening.Knockdown of RNF126 dramatically decreased cell viability in these cancer cell lines.