PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription

PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription
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DOI:
10.1016/j.febslet.2013.09.001
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发表时间:
2013-10-11
期刊:
影响因子:
3.5
通讯作者:
Kamisaki, Yoshinori
Kamisaki, Yoshinori
中科院分区:
生物学3区
文献类型:
--
作者:
Kamano, Yuya;Saeki, Makio;Kamisaki, Yoshinori

文献摘要

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PIH 1D 1是R2 TP复合物的定义成分。最近,R2 TP已被报道稳定mTOR(雷帕霉素的哺乳动物靶标),细胞生长和蛋白质合成的重要调节剂。已经鉴定了mTOR的两种复合物mTORC 1和mTORC 2。我们证明,PIH 1D 1的免疫沉淀(IP)导致Raptor(mTORC 1特异性)的co-IP,但不是Rictor(mTORC 2特异性),PIH 1D 1的敲低降低了mTORC 1组装,S6激酶磷酸化(mTORC 1活性的指标)和rRNA转录,而不影响人乳腺癌MCF-7细胞中的mTORC 2。此外,我们提供的证据表明,PIH 1D 1在各种乳腺癌细胞系中过表达。这些研究结果共同表明,PIH 1D 1可能在乳腺癌mTORC 1调节中发挥重要作用.Structured summary of protein interactions:mTOR physically interacts with PIH 1D 1 and Raptor by antitag coimmunoprecipitation(View interaction)Rictor physically interacts with mTOR and Tel 2 by antibait coimmunoprecipitation(View interaction)Raptor physically interacts with Tel 2,PIH 1D 1 and mTOR by antibait coimmunoprecipitation(View interaction)PIH 1D 1 physically interacts with mTOR and Raptor by antibait coimmunoprecipitation(View interaction)(C)2013 Federation of European Biochemical Societies.由Elsevier B出版。V.保留所有权利。
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.Structured summary of protein interactions:mTOR physically interacts with PIH1D1 and Raptor by anti tag coimmunoprecipitation (View interaction)Rictor physically interacts with mTOR and Tel2 by anti bait coimmunoprecipitation (View interaction)Raptor physically interacts with Tel2, PIH1D1 and mTOR by anti bait coimmunoprecipitation (View interaction)PIH1D1 physically interacts with mTOR and Raptor by anti bait coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.