Thus, the decrease in levels of activated Rac1 in HACE1 overexpressing MCF7 cells is due to the proteosomal degradation of polyubiquitination of Rac1 at lysine 147 by HACE1. Although breast cancer cell lines have reduced levels of HACE1 compared with their normal counterparts (Supplementary Figure 3), we wished to see whether the reduction of HACE1 contributes to the their initial transformation. Here, HACE1 is linked to breast cancer.