title: PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.
abstract: PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been reported to stabilize mTOR (mammalian target of rapamycin), an important regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2 specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase phosphorylation (indicator of mTORC1 activity), and rRNA transcription without affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These findings collectively suggest that PIH1D1 may have an important role in mTORC1 regulation in breast cancers.
authors.affiliation: Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan; Department of Fixed Prosthodontics, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kamano
authors.forename: Makio
authors.initials: M
authors.lastname: Saeki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kakihara
authors.forename: Walid A
authors.initials: WA
authors.lastname: Houry
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yatani
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamisaki
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012335:RNA, Ribosomal / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D046912:Multiprotein Complexes; C555143:PIH1D1 protein, human; D012335:RNA, Ribosomal; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Breast cancer; Monad; PIH1D1; R2TP; Ribosome; mTOR