Hsc70 is required for the activation of Heat Shock Factor 1 (HSF1) in mammalian cells

Abstract

Heat shock factor (HSF1)은 다양한 physiological stress에 반응하여 세포내에서 중요한 역할을 수행한다. 그러나 HSF1의 조절기전에 대해서는 정확하게 알려져 있지 않다. 본 연구자는 HSF1 interacting protein으로 Hsc70을 Mass spectrometry를 이용하여 확인하였다. Hsc70은 heat 처리된 세포내에서 HSF1 기전에 관여하여 target gene 발현을 증가시켰으며, 반면 Hsc70에 대한 siRNA를 이용하여 세포내에서 Hsc70의 발현을 저해시키면 stress에 의한 HSF1의 활성이 점차 감소하였다. Hsc70의 저해는 HSF1의 target gene 발현을 감소시켰고, stress에 의해 유도되는 apoptosis의 저해 능력 또한 감소시켰다. 이들 결과에서, Hsc70가 HSF1조절에 중요한 인자임을 보여주고 있다.|Heat shock factor1 (HSF1) plays an essential role in mediating cellular response to diverse forms of physiological stresses. However, the molecular process of HSF1 modulated by its interacting protein was poorly understood. Here we identified Hsc70 as an interacting protein of HSF1 using Mass spectrometry. HSF1 exists in unstressed cells as a complexed form with Hsc70. Interestingly, Hsc70 was required for the regulation of HSF1 during heat stress and subsequent target gene expression in mammalian cells. Moreover, cells transfected with siRNAs targeted to Hsc70 showed greatly decreased activation of HSF1. The expression of HSF1 target gene was reduced by inhibition of Hsc70 and showed loss of cell protection ability by stress-induced apoptosis. These results indicate that Hsc70 is necessary and sufficient for the regulation of HSF1.