In the present study, we demonstrated that CUL4B regulates extensive gene networks in breast cancer cells through interactions with multiple corepressor complexes; E‐cadherin, AXIN2, and ERα were regulated by the CRL4B/NuRD(MTA1) complex; ATM, p21, and p18 by the CRL4B/SIN3A complex; BDNF, LAMA5, and ROBO3 by the CRL4B/CoREST complex; and AKT1, TRAF4, and TSC1 by the CRL4B/NCoR/HDAC3 complex. The gene discussed is HDAC3; the disease is breast cancer.