For instance, the level of polyubiquitinated proteins is increased in response to ISG15 knockdown in ZR-75-1 breast cancer cells [24], which could result from a competition between ISG15 and ubiquitin for common E2 enzymes, such as UbcH8 [38], [39], and UbcH6 [40]. This evidence concerns the gene ISG15 and breast carcinoma.