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.
FEBS Lett. 2013 Oct 11;587(20):3303-8. doi: 10.1016/j.febslet.2013.09.001. Epub 2013 Sep 11.
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.
PIH1D1 是 R2TP 复合物的标志性组成部分。最近，有报道称 R2TP 可以稳定 mTOR（雷帕霉素的哺乳动物靶标），mTOR 是细胞生长和蛋白质合成的重要调节剂。已经鉴定出两种 mTOR 复合物，mTORC1 和 mTORC2。我们证明，PIH1D1 的免疫沉淀（IP）导致 Raptor（mTORC1 特异性）而非 Rictor（mTORC2 特异性）的共免疫沉淀，并且 PIH1D1 的敲低会降低 mTORC1 组装、S6 激酶磷酸化（mTORC1 活性的指标）和 rRNA 转录，而不会影响人乳腺癌 MCF-7 细胞中的 mTORC2。此外，我们提供的证据表明 PIH1D1 在各种乳腺癌细胞系中过表达。这些发现共同表明 PIH1D1 在乳腺癌中 mTORC1 调节中可能发挥重要作用。
