Prohibitin regulates mTOR pathway via interaction with FKBP8
Jiahui Zhang , Yanan Yin , Jiahui Wang , Jingjing Zhang , Hua Liu , Weiwei Feng , Wen Yang , Bruce Zetter , Yingjie Xu
Front. Med. ›› 2021, Vol. 15 ›› Issue (3) : 448 -459.
Prohibitin regulates mTOR pathway via interaction with FKBP8
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.
prohibitin 1 / FKBP8 / mTOR / cell proliferation / cancer
Higher Education Press
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