The mouse stress-induced protein (SIP) mRNA is activated in the pancreas with acute pancreatitis and in several cell lines in response to various stress agents. The SIP gene is alternatively spliced, generating two proteins (SIP'8 and SIP27). Both proteins, located mainly in the nucleus, promote cell death when overexpressed in vitro. We show that induction by stress agents of the expression of SIP18 and SIP27 mRNAs, observed in human- and mouse-derived cell lines, is absent from cells with deleted, mutated or inactive p53, suggesting that regulation of SIP gene expression is dependent on p53. That hypothesis is consistent with the presence of a functional p53-response element within the promoter region of the mouse SIP gene and confirmed by the induction of SIP mRNA expression in mouse embryo fibroblasts upon activation of a p53-dependent pathway by transfection with rasV12 or rasV12/E1A. In conclusion, SIP being a proapoptotic gene induced through p53 activation could be a stress-induced gene with antitumour properties.

中文翻译：

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应激诱导蛋白（SIP）的P53依赖性表达。

小鼠应激诱导的蛋白质（SIP）mRNA在胰腺急性胰腺炎和多种细胞系中被激活，以响应各种应激因素。SIP基因被剪接，产生两种蛋白质（SIP'8和SIP27）。两种蛋白质（主要位于细胞核中）在体外过度表达时都会促进细胞死亡。我们显示，在人和小鼠衍生的细胞系中观察到的由胁迫因子诱导的SIP18和SIP27 mRNA的表达在缺失，突变或失活的p53的细胞中不存在，这表明SIP基因表达的调节依赖于p53 。该假设与小鼠SIP基因启动子区域内功能性p53反应元件的存在是一致的，并且通过转染rasV12或rasV12激活了p53依赖性途径后，小鼠胚胎成纤维细胞中SIP mRNA表达的诱导证实了这一假设。 / E1A。总之，SIP是通过p53激活诱导的促凋亡基因，可能是具有抗肿瘤特性的应激诱导基因。