ESR1 and breast cancer: Following CHIP transfection, BC cell lines demonstrated increased ESR1 proteasomal degradation and decreased ESR1-mediated gene transcription compared to those with CHIP depletion.[11] ESR1 is maintained in a ligand-binding conformation by HSP90-based chaperones.[12] and HSP90 inhibitors, such as geldanamycin (GA), enhance the ESR1-CHIP interaction and promote degradation through the ubiquitin-proteasome pathway.[13, 14] In this way, CHIP can influence ESR1-receptor profiles and hormone responsiveness.