Human Fas-associated Factor 1 Interacts with Heat Shock Protein 70 and Negatively Regulates Chaperone Activity

다국어 초록 (Multilingual Abstract)

We examined the cell death-inducing property of human Fas-associated factor 1 (hFAFl) in the hat shock signaling pathway. By employing co-irnmunoprecipitation and peptide mass fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we found that hFAF1 binds to the 70-KDa heat shock protein family (Hsc70/Hsp70). Interaction mapping indicated that the 82-180 sequence of kFAF1 directly binds to the N-terminal region containing soquence 1-120 of Hsc70/Hsp70. This binding is very tight regardless of ATP and heat shock treatment. Hsc70/Hsp70 and hFAFl co-localized in the cytosol and nucleus and concentrated to the perinuclear region by heat shoclt treatment. We examined how hFAFl regulates Hsp70 function, and found that hFAF1 inhibited the Hsp70 chaperone activity of refolding denatured protein substrates, accelerated heat shock-induced SAPK/JNK activation, and raised heat shook-induced cell death in a binding dependent manner. These results suggest that hFAF1 prevents cells from recovery after stress 1)y binding to and inhibiting the chaperone activity of Hsp70.