Prohibitin regulates mTOR pathway via interaction with FKBP8 / 医学前沿

The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a "switch" type regulator. We identified through immunoprecipitation-mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

Effect of all-trans retinoic acid on expressions of Prohibitin1 and Prohibitin2 in hypoxic damage of renal tubular epithelial cells / 中华实用儿科临床杂志

Objective To investigate the effect of all-trans retinoic acid(ATRA) on the expressions of Prohibitin1 (PHB1) and Prohi-bitin2 (PHB2) in hypoxic damage of renal tubular epithelial cells (RTEC).Methods Rat proximal tubular epithelial cell line NRK-52E culture was performed in the 37 ℃ 50 mL/L carbon dioxide incubator with mixture medium of fetal bovine serum and double-antibody(100 mL medium plus 5 mL fetal calf serum and 1 mL double-antibody).After 3 times cell propagation,the cells were divided into 3 groups:normal group,model group and ATRA intervention group.The normal group wasn't disposed,and the model group was put into vacuum tank filled with hypoxic gas(950 mL/L nitrogen and 50 mL/L carbon dioxide) to induce a hypoxic damage of RTEC.The ATRA intervention group was added 0.1 μmol/L ATRA and was treated with hypoxic gas as model group.After 24 h and 36 h,the mRNA expressions of PHB1,PHB2 and transforming growth factor-β1 (TGF-β1) were measured by using real-time PCR method,and the protein expressions of PHB1,PHB2 and TGF-β1 were detected by using Western blot method.Results 1.Compared with normal group,NRK-52E cells PHB1,PHB2 protein expressions and mRNA expressions at 2time points(24 h,36 h) were significantly decreased in model group and ATRA intervention group (all P ＜ 0.05),and the longer hypoxia time,the lower expression value.Compared with model group,NRK-52E cells PHB1 and PHB2 protein expressions and mRNA expressions in ATRA intervention group were increased significantly at 2 time points (all P ＜ O.05).2.Compared with normal group,NRK-52E cells TGF-β1 expressions and mRNA expressions at 2 time points(24 h,36 h) were significantly increased in model group and ATRA intervention group(all P ＜ 0.05),and the longer hypoxia time,the higher expression value;Compared with model group,NRK-52E cells TGF-β1 protein expressions and mRNA expressions in ATRA intervention group were decreased significantly at 2 time points(all P ＜ 0.05).Conclusions ATRA can significantly up-regulate the mRNA expressions and protein expressions of PHB1 and PHB2 in hypoxic damage of RTEC,and ATRA may have a protective effect against hypoxic damage.