MLN4924, a selective inhibitor of the key neddylation enzyme NEDD8 Activation Enzyme (NAE1), shows higher sensitivity to both BRCA1-wild type and -mutant TNBCs compared to other breast cancer subtypes. We used both BRCA1 wild type (MDA-MB-231, MDA-MB-468, and SUM159PT) and BRCA1-mutated (MDA-MB-436) TNBC cell lines and observed that, as opposed to PARP inhibitor, both BRCA1-wild type and mutant cell lines show equal sensitivity to MLN4924 (All IC50 below 1 µM, Figure 1A)...combining MLN4924 with cisplatin will have greater therapeutic efficacy for a wider group of TNBC patients....Collectively, our results established the molecular mechanism by which MLN4924 induces TNBC cell death and enhances cisplatin sensitivity, provided the rationale of combining MLN4924 with cisplatin in both BRCA1-wild type and mutant TNBCs, and identified a cancer genetic background where this combination will be more effective.