| Summary: | 碩士 === 國立臺灣大學 === 免疫學研究所 === 87 === Heat shock proteins of HSP70 family are molecular chaperones whose expression are highly induced by stress condition. Overexpression of HSP70s protect cells from apoptosis induced by subsequent stresses. Recent studies reveal that HSP70s protect cell from stress-induced cell death not only by preventing the aggregation of damage proteins but also by direct inhibition on apoptotic signaling pathway, such as JNK activation and pro-caspase-3 processing. In this study, we examined the effect of Hsc70, one member of HSP70 family, on T cell activation and Fas-induced apoptosis. We observed that the overexpression of Hsc70 inhibited the activation of JNK activated by MEKK. Overexpression of Hsc70 also inhibited the activation of IL-2 promoter, which can be attributed to the suppression of AP-1 and NF-kB, two transcription factors that are required for IL-2 production during T cell activation. We found that Hsc70 partially protected cell from Fas-induced apoptosis when Hsc70 was either transiently or prolonged expressed. Furthermore, overexpression of Hsc70 partially inhibited FADD-induced cell death, indicating that Hsc70 protects cell from death signals downstream of Fas signal receptor. However, we failed to produce cell clones with constitutive Hsc70 overexpression. This might be due to the negative role of Hsc70 on cell growth and proliferation, forcing cells to adapt by downregulating the endogenous Hsc70.
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