Pag, a putative tumor suppressor, interacts with the Myc Box II domain of C-myc and selectively alters its biological function and target gene expression
Pag, a putative tumor suppressor, interacts with the Myc Box II domain of C-myc and selectively alters its biological function and target gene expression
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DOI：
10.1074/jbc.m206066200
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发表时间：
2002-11-08
影响因子：
4.8
通讯作者：
Prochownik, EV
中科院分区：
文献类型：
--
作者：
Mu, ZM;Yin, XY;Prochownik, EV
高度保守的Myc Box II （MBII）结构域对c-Myc的转化和转录调控至关重要。酵母双杂交筛选鉴定Pag是一个与mbii相互作用的蛋白。Pag是过氧化物还氧蛋白家族的一员，先前已报道与c-Abl癌蛋白结合并抑制其细胞抑制特性。我们现在表明，Pag促进细胞大小增加，并赋予促凋亡表型，这是异位c-Myc过表达的两个标志性特征。Pag和c-Myc也赋予抗氧化应激能力，这是后一种蛋白质以前未被认识到的特性。相反，Pag抑制过表达c-Myc的成纤维细胞的肿瘤发生，导致c-Myc靶基因调控的广泛但选择性丧失。因此，Pag是一种mbii相互作用蛋白，可以模仿或增强c-Myc的某些特性，同时抑制其他特性。这些特征，加上之前发现的与c-Abl的相互作用，为Pag作为肿瘤抑制因子的观点提供了支持。
The highly conserved Myc Box II (MBII) domain of c-Myc is critically important for transformation and transcriptional regulation. A yeast two-hybrid screen identified Pag as a MBII-interacting protein. Pag, a member of the peroxiredoxin family, has been reported previously to bind to and inhibit the cytostatic properties of the c-Abl oncoprotein. We now show that Pag promotes increased cell size and confers a proapoptotic phenotype, two hallmark features of ectopic c-Myc overexpression. Pag and c-Myc also confer resistance to oxidative stress, a previously unrecognized property of the latter protein. In contrast, Pag inhibits tumorigenesis by c-Myc-overexpressing fibroblasts and causes a broad but selective loss of c-Myc target gene regulation. Pag is therefore an MBII-interacting protein that can either mimic or enhance some of the c-Myc properties while at the same inhibiting others. These features, along with the previously identified interaction with c-Abl, provide support for the idea that Pag functions as a tumor suppressor.