Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14.
Regulation of phosphoglucose isomerase/autocrine motility factor activities by the poly(ADP-ribose) polymerase family-14.
复制标题
聚（ADP-核糖）聚合酶家族 14 对磷酸葡萄糖异构酶/自分泌运动因子活性的调节。
DOI：
10.1158/0008-5472.can-07-1586
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发表时间：
2007
期刊：
影响因子：
11.2
通讯作者：
Raz,Avraham
中科院分区：
文献类型：
--
作者：
Yanagawa,Takashi;Funasaka,Tatsuyoshi;Tsutsumi,Soichi;Hu,Huankai;Watanabe,Hideomi;Raz,Avraham
磷酸葡萄糖异构酶（PGI; EC 5.3.1.9）是糖酵解和糖异生所必需的普遍存在的细胞溶质酶。PGI是一种多功能二聚体蛋白，其在细胞外充当细胞因子[自分泌运动因子（AMF）]，通过与其细胞表面受体gp 78/AMF受体（AMFR）结合而引发促有丝分裂、运动原和分化功能。AMFR包含具有RING-H2和亮氨酸拉链基序的七跨膜结构域，其显示泛素蛋白连接酶（E3）活性，并且暴露在内质网表面上。PGI/AMF和AMFR的增强表达与肿瘤进展和转移有关，并且PGI/AMF的细胞内结合伴侣预期部分调节其多种生物学功能。因此，我们使用酵母双杂交系统筛选cDNA文库，以寻找相互作用的蛋白质，并报告发现聚（ADP-核糖）聚合酶-14（PARP-14）是PGI/AMF的结合伴侣。通过免疫共沉淀和免疫定位证实PARP-14-PGI/AMF相互作用。我们还报道了PGI/AMF降解主要受泛素-溶酶体系统的调节，RNA干扰实验表明PARP-14抑制PGI/AMF泛素化，从而有助于其稳定和分泌。这种新表征的PARP-14蛋白应有助于理解PGI/AMF细胞内功能的调节，并可能为抑制PGI/AMF诱导的肿瘤细胞转移和侵袭提供新的治疗靶点。[Cancer Res 2007;67（18）：8682-9]
Phosphoglucose isomerase (PGI; EC 5.3.1.9) is a ubiquitous cytosolic enzyme essential for glycolysis and gluconeogenesis. PGI is a multifunctional dimeric protein that extracellularly acts as a cytokine [autocrine motility factor (AMF)] eliciting mitogenic, motogenic, and differentiation functions through binding to its cell surface receptor gp78/AMF receptor (AMFR). AMFR contains a seven-transmembrane domain with RING-H2 and leucine zipper motifs showing ubiquitin protein ligase (E3) activity and is exposed on the endoplasmic reticulum surface. Augmented expressions of both PGI/AMF and AMFR have been implicated in tumor progression and metastasis, and an intracellular binding partner of PGI/AMF is expected to regulate in part its diverse biological functions. Thus, we screened a cDNA library using a yeast two-hybrid system to search for interacting protein(s) and report on the finding of poly(ADP-ribose) polymerase-14 (PARP-14) to be a binding partner with PGI/AMF. PARP-14–PGI/AMF interaction was confirmed by coimmunoprecipitation and immunolocalization. We also report that PGI/AMF degradation is mainly regulated by the ubiquitin-lysosome system and RNA interference experiments revealed that PARP-14 inhibits PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. This newly characterized PARP-14 protein should assist in understanding the regulation of PGI/AMF intracellular function(s) and may provide a new therapeutic target for inhibition of PGI/AMF inducing tumor cell migration and invasion during metastasis. [Cancer Res 2007;67(18):8682–9]