Heat stress increases the expression of ZBP1 through HSF1
热应激通过HSF1上调ZBP1的表达
ZBP1 is an interferon-inducible factor (21), and heat stress up-regulated the expression of ZBP1 in L929 cells and mouse macrophages in a manner similar to that of type 1 interferon.
ZBP1是一种干扰素诱导因子,在L929细胞和小鼠巨噬细胞中,热应激以类似于1型干扰素的方式上调ZBP1的表达。
Furthermore, heat stress stimulated ZBP1 transcription in the lung, liver, kidney, and intestine (Fig. 5E and fig. S8C). We used the bioinformatics tool Jaspar to analyze the promoter region of ZBP1 and identified a predicted binding site for heat shock transcription factor1 (HSF1) (Fig. 5F), which is activated by heat stress (22) . Deletion of the putative HSF1 binding site prevented the increase in transcriptional activation through the ZBP1 promoter after heat stress (Fig. 5F).
另外,热应激刺激ZBP1在肺脏,肝脏,肾脏和肠道内的转录。我们应用JASPAR去分析了ZBP1的启动子区域,并确定了和HSF1的预测结合位点,该位点是由热应激激活的。将预测的HSF1结合位点删除会减少热应激后通过ZBP1启动子结合而激活的转录增加。
Heat stress enhanced HSF1 activation and occupancy at the HSF1 binding site in the ZBP1 promoter(Fig. 5G and fig. S8, D to F). Deletion of HSF1 inhibited a heat stress–induced increase in ZBP1 expression and cell death (Fig. 5H, fig.S8G, and fig. S9A).
热应激会加强HSF1的激活,并且占据ZBP1的启动子上的HSF1的结合位点。HSF1的缺失抑制了热应激诱导的ZBP1的表达和细胞死亡
In response to heat stress,HSF1 regulated the expression of heat shock proteins (HSPs) (fig. S9B) (22). HSP90 enhances TNF-induced necroptosis through the promotion of MLKL oligomerization and activation(23, 24).
为响应热应激,HSF1调节HSP的表达。HSP90通过促进MLKL寡聚化和活化来增强TNF诱导的坏死,
However, depletion of HSP90 did not affect heat stress–induced phosphorylation of RIPK3 or MLKL and cell death (fig. S9, C and D). This discrepancy might be because of the different stimuli used (TNF versus heat stress). These data establish that heat stress increases the expression of ZBP1 through HSF1.
然而,HSP90的缺失不能影响热应激诱导的RIPK3或MLKL的磷酸化和细胞死亡。这种差异可能是因为不同的刺激(TNF和热应激)。这些数据证明了热应激通过HSF1来增加ZBP1的表达。
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