A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis
A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis
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DOI：
10.1023/a:1011392811628
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发表时间：
2001-06-01
期刊：
影响因子：
7.2
通讯作者：
Maxwell, SA
中科院分区：
文献类型：
--
作者：
Nelson, V;Davis, GE;Maxwell, SA
最近报道，P53蛋白能够通过一种不依赖于其反式激活功能的途径来介导细胞凋亡。我们报道了活化的STAT家族的蛋白抑制因子PIASy在不影响其诱导H1299非小细胞肺癌细胞株凋亡的情况下，抑制了P53‘S的反式激活功能。在酵母双杂交实验中，PIASy与PIASy结合，并与哺乳动物细胞免疫沉淀物中的PIASy形成复合物。PIASy抑制细胞核提取物中P53的DNA结合活性，并阻断P53诱导H1299细胞Bax和p21(Waf1/Cip1)表达的能力。由于PIASy抑制了P53‘S反式激活p21/荧光素酶报告结构的能力，因此对P53介导的bax和p21诱导的阻断处于反式激活水平。PIASy不影响P53表达上调的H1299细胞的凋亡率。PIASy似乎调节P53介导的功能，并可能引导P53进入反式激活非依赖的凋亡模式。
The p53 protein has recently been reported to be capable of mediating apoptosis through a pathway that is not dependent on its transactivation function. We report here that the PIASy member of the protein inhibitor of activated STAT family inhibited p53's transactivation function without compromising its ability to induce apoptosis of the H1299 nonsmall cell lung carcinoma cell line. The p53 protein bound to PIASy in yeast two-hybrid assays and coprecipitated in complexes with p53 in immunoprecipitates from mammalian cells. PIASy inhibited the DNA-binding activity of p53 in nuclear extracts and blocked the ability of p53 to induce expression of two of its target genes, Bax and p21(Waf1/Cip1), in H1299 cells. The block in p53-mediated induction of Bax and p21 was determined to be at the level of transactivation, since PIASy inhibited p53's ability to transactivate a p21/luciferase reporter construct. PIASy did not effect the incidence of apoptosis in H1299 cells upregulated for p53. PIASy appears to regulate p53-mediated functions and may direct p53 into a transactivation-independent mode of apoptosis.