title: Histone acetyltransferase Hbo1 destabilizes estrogen receptor α by ubiquitination and modulates proliferation of breast cancers.
abstract: The estrogen receptor (ER) is a key molecule for growth of breast cancers. It has been a successful target for treatment of breast cancers. Elucidation of the ER expression mechanism is of importance for designing therapeutics for ER-positive breast cancers. However, the detailed mechanism of ER stability is still unclear. Here, we report that histone acetyltransferase Hbo1 promotes destabilization of estrogen receptor α (ERα) in breast cancers through lysine 48-linked ubiquitination. The acetyltransferase activity of Hbo1 is linked to its activity for ERα ubiquitination. Depletion of Hbo1 and anti-estrogen treatment displayed a potent growth suppression of breast cancer cell line. Hbo1 modulated transcription by ERα. Mutually exclusive expression of Hbo1 and ERα was observed in roughly half of the human breast tumors examined in the present study. Modulation of ER stability by Hbo1 in breast cancers may provide a novel therapeutic possibility.
authors.affiliation: Department of Biochemistry, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iizuka
authors.forename: Takao
authors.initials: T
authors.lastname: Susa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Mimi
authors.initials: M
authors.lastname: Tamamori-Adachi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajitani
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okinaga
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
authors.forename: Tomoki
authors.initials: T
authors.lastname: Okazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering; D013629:Tamoxifen / Q000494:pharmacology; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D013629:Tamoxifen; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human