Since inhibition of UPS pathway using MG-132 can cause dramatic accumulation of cellular BRCA1, it is possible that UPS could be a major pathway for BRCA1 degradation, and other yet unidentified E3 ligases that are responsible for degrading BRCA1 might exist and play a crucial role in a subset of breast cancers 21. The gene discussed is BRCA1; the disease is breast carcinoma.