［原著］Heat Stress Promotes the Degradation of p53 and p300/CBP-associated Factor in Murine Embryonic Fibroblasts

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Heat stress, like genotoxic- and oxidative-stresses, has been reported to induce nuclear accumulation of p53 and its activation. However, exposure of mouse embryonic fibroblasts to elevated temperature caused insolubilization of nuclear P53 together with its co-activator, P300/CBP-associated factor (PCAF). The insolublized proteins were translocated to the perinuclear region by CRMl-dependent export system, Which was inhibited by leptomycin B. On the other hand, other co-activators, CBP and p300 remained soluble in nucleus. The insolubilization of the two proteins also occurred in other cellines, when the cells were heat－exposed. After the heat stress, the insolublized p53 and PCAF in the cells were degraded by proteasome, which was inhibited by pretreatment of the cells with MG-132. During the degradation, Hsp70-expression was initiated and subsequently newly synthesized p53 and PCAF reappeared as soluble forms in nucleus. These results indicate that nuclear p53 and PCAF transiently disappearpr prior the induction of Hsp70-expression in response to heat stress. Conversely, genotoxic-and oxidative-stress induced neither the loss of these two proteins nor Hsp70-expression.Since p53 functions as a proapoptotic factor and a repressor of Hsp70-expression, the transient disappearance of nuclear p53 and PCAF may partly contribute to the cell survival through the enhancement of Hsp70-expression.