[Heat shock proteins: new target in cytoprotective and tumor therapy].
Heat shock proteins (HSPs) form the most ancient defense system in all living organisms. These proteins act as molecular chaperones by helping the refolding of misfolded proteins and assisting their elimination if they become irreversibly damaged. HSPs interact with a number of cellular systems and form efficient cytoprotective mechanisms. HSPs allow cells to adapt to gradual changes in their environment and to survive in otherwise lethal conditions. The events of cell stress and cell death are linked, and HSPs induced in response to stress appear to function at key regulatory points in the control of apoptosis. HSPs include antiapoptotic and proapoptotic proteins that interact with a variety of cellular proteins. Their expression levels can determine the fate of the cell in response to death stimulus. On the other hand, HSPs are overexpressed in tumor cells, and the inhibition of HSP90 has recently been regarded as a very promising tool to combat various cancers. HSPs can be secreted to circulatory system from a variety of cell types in response to stress. The secreted exogenous proteins act as cytokines and have potential modulatory functions in immune system. Cell surface-bound HSP70 can render tumor cell more sensitive to natural killer cell-mediated cytolytic attack. Therefore, modulator of chaperone activities is becoming a new target of drug development, such as in apoptosis and tumor immunity fields.
Bao
Xiu-Qi
XQ
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China. baoxiuqi@imm.ac.cn
Liu
Geng-Tao
GT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000191:economics / Q000379:methods / Q000639:trends*; D004354:Drug Screening Assays, Antitumor; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D004364:Pharmaceutical Preparations