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Deptor:不仅仅是一种mTOR抑制剂。

Deptor: not only a mTOR inhibitor.

作者信息

Catena Valeria, Fanciulli Maurizio

机构信息

SAFU, Department of Research, Advanced Diagnostics, and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144, Rome, Italy.

出版信息

J Exp Clin Cancer Res. 2017 Jan 13;36(1):12. doi: 10.1186/s13046-016-0484-y.

Abstract

Deptor is an important protein that belongs to the mTORC1 and mTORC2 complexes, able to interact with mTOR and to inhibit its kinase activity. As a natural mTOR inhibitor, Deptor is involved in several molecular pathways, such as cell growth, apoptosis, autophagy and ER stress response. For this reason, Deptor seems to play an important role in controlling cellular homeostasis. Despite several recent insights characterizing Deptor functions and regulation, its complete role within cells has not yet been completely clarified. Indeed, quite recently, Deptor has been associated with chromatin, and it has been demonstrated having a role in transcriptional regulation, controlling in such way endoplasmatic reticulum activity.From all these observations it is not surprising that Deptor can behave either as an oncogene or oncosuppressor, depending on the cell- or tissue-contexts. This review highlights recent progresses made in our understanding of the many activities of Deptor, describing its transcriptional and post-transcriptional regulation in different cancer cell types. Moreover, here we discuss the possibility of using compounds able to inhibit Deptor or to disrupt its interaction with mTOR as novel approaches for cancer therapy.

摘要

Deptor是一种重要的蛋白质,属于mTORC1和mTORC2复合物,能够与mTOR相互作用并抑制其激酶活性。作为一种天然的mTOR抑制剂,Deptor参与多种分子途径,如细胞生长、凋亡、自噬和内质网应激反应。因此,Deptor似乎在维持细胞稳态中发挥重要作用。尽管最近有一些关于Deptor功能和调控的见解,但它在细胞内的完整作用尚未完全阐明。事实上,就在最近,Deptor已与染色质相关联,并且已证明它在转录调控中发挥作用,从而控制内质网活性。从所有这些观察结果来看,Deptor根据细胞或组织背景既可以作为癌基因也可以作为肿瘤抑制基因发挥作用也就不足为奇了。本综述强调了我们在理解Deptor的多种活性方面取得的最新进展,描述了其在不同癌细胞类型中的转录和转录后调控。此外,我们在此讨论使用能够抑制Deptor或破坏其与mTOR相互作用的化合物作为癌症治疗新方法的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db16/5237168/6ef43d1531b9/13046_2016_484_Fig1_HTML.jpg

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