Li Canrong, Yi Yuguo, Ouyang Yingyi, Chen Fengzhi, Lu Chuxin, Peng Shujun, Wang Yifan, Chen Xinyu, Yan Xiao, Xu Haolun, Li Shuiming, Feng Lin, Xie Xiaoduo
School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
College of Life Sciences and Oceanography, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, China.
Cell Biosci. 2024 Jun 1;14(1):68. doi: 10.1186/s13578-024-01250-4.
Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is an effective therapeutic target for diseases such as cancer, diabetes, aging, and neurodegeneration. However, an efficient tool for monitoring mTORC1 inhibition in living cells or tissues is lacking.
We developed a genetically encoded mTORC1 sensor called TORSEL. This sensor changes its fluorescence pattern from diffuse to punctate when 4EBP1 dephosphorylation occurs and interacts with eIF4E. TORSEL can specifically sense the physiological, pharmacological, and genetic inhibition of mTORC1 signaling in living cells and tissues. Importantly, TORSEL is a valuable tool for imaging-based visual screening of mTORC1 inhibitors. Using TORSEL, we identified histone deacetylase inhibitors that selectively block nutrient-sensing signaling to inhibit mTORC1.
TORSEL is a unique living cell sensor that efficiently detects the inhibition of mTORC1 activity, and histone deacetylase inhibitors such as panobinostat target mTORC1 signaling through amino acid sensing.
哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）是癌症、糖尿病、衰老和神经退行性疾病等疾病的有效治疗靶点。然而，目前缺乏一种在活细胞或组织中监测mTORC1抑制作用的有效工具。
我们开发了一种名为TORSEL的基因编码mTORC1传感器。当4EBP1发生去磷酸化并与eIF4E相互作用时，该传感器的荧光模式会从弥散型变为点状。TORSEL能够特异性地检测活细胞和组织中mTORC1信号通路的生理、药理和基因抑制作用。重要的是，TORSEL是用于基于成像的mTORC1抑制剂视觉筛选的有价值工具。利用TORSEL，我们鉴定出了选择性阻断营养感应信号以抑制mTORC1的组蛋白去乙酰化酶抑制剂。
TORSEL是一种独特的活细胞传感器，可有效检测mTORC1活性的抑制作用，而诸如帕比司他等组蛋白去乙酰化酶抑制剂通过氨基酸感应靶向mTORC1信号通路。
