Intrinsic ubiquitin E3 ligase activity of histone acetyltransferase Hbo1 for estrogen receptor α.

Estrogen receptors (ER) are important transcription factors to relay signals from estrogen and to regulate proliferation of some of breast cancel's. The cycling of estrogen-induced DNA binding and nbiqiiitin-linked proteolysis of ER potentiates ER-mediated transcription. Indeed, several transcriptional coactivators for ER-dependent transcription nbiqnitinate ER. Histone acetyltransferase (HAT) Hbol/KAT7/MYST2, involved in global histone acetylation, DNA replication, transcription, and cellular proliferation, promotes proteasome-dependent degradation of ERα through nbiqnitination. However, molecular mechanism for nbiqiiitination of ER/* by Hbol is unknown. Here we report the intrinsic nbiquitin E3 Ugase activity of Hbol toward the ERαr. The ligand, estradiol-17β, inhibited E3 ligase activity of Hbol for ERα in vitro, whereas hyperactive ERα mutants from metastatic breast cancers resistant to hormonal therapy, were better substrates for ERα nbiqnitination by Hbol. Hbol knock-down caused increase in ERα: expression. Hbol is another ERa coactivator that ubiquitinates ERα. [ABSTRACT FROM AUTHOR]