RAC1 and cancer: Given that disrupted dimerization significantly enhanced HACE1 activity, we surmised that misregulation of HACE1 activity by cancer‐associated mutations may lead to abnormal substrate binding and ubiquitination activity.[8, 15, 32] To this end, we first examined the binding of the target substrate RAC1 to HACE1 and used amide HDX–MS to map the RAC1 interaction sites in the HACE1–RAC1 complex.