BARD1 and breast cancer: The RING domain and the substrate-recruiting module of the RING E3 ligase can be found in a single polypeptide, as in the case of CBL (Casitas B-lineage lymphoma), or in separate subunits of a multi-complex E3s, as for the heterodimer of BRCA1 (breast cancer 1) and BARD1 (BRCA1-associated RING domain 1), Cullin–RING ligases, and APC [34].