Abstract：Abstract: Due to oncogene mutation and stressful environments including hypoxia, nutritional stress and pH stress, tumor cells are often subjected to endoplasmic reticulum (ER) protein folding stress. Cellular adaptation to ER stress is achieved by the activation of unfolded protein response (UPR). There are three key transmembrane proteins on the ER membrane to sense and process unfolded protein signals. The outcome of UPR activation involves transient attenuation of protein synthesis, increased capacity for protein trafficking through the ER, protein folding and transport, and increased protein degradation through ER-associated degradation (ERAD). However, above a certain threshold, chronic UPR results in apoptosis. Heat shock protein 90 (Hsp90) is an evolutionarily conserved molecular chaperone, involving in stabilization and activation of over 300 client proteins. Hsp90 inhibitors disrupt folding and maturation of the client proteins, and cause degradation of inositol-requiring enzyme 1α (IRE1α), the essential UPR signal. So far, the inhibitors could effectively elicit UPR-mediated apoptosis of secretory tumors like multiple myeloma and RAS-driven tumors.
引用本文:
申跃武, 韩钢杰, 马亚洪, 蔡晓明, 刘 云, 母 波. Hsp90抑制剂对未折叠蛋白反应作用的研究进展[J]. 生命科学研究, 2017, 21(1): 64-68. SHEN Yue-Wu, HAN Gang-Jie, MA Ya-Hong, CAI Xiao-Ming, LIU Yun, MU Bo. Progresses on Hsp90 Inhibitor Targeting Unfolded Protein Response. Life Science Research, 2017, 21(1): 64-68.
2017,Vol. 21
