RNF13: a novel RING-type ubiquitin ligase over-expressed in pancreatic cancer

RNF13: a novel RING-type ubiquitin ligase over-expressed in pancreatic cancer
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RNF13:一种在胰腺癌中过表达的新型 RING 型泛素连接酶

DOI:
10.1038/cr.2008.285
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发表时间:
2009-03
期刊:
影响因子:
44.1
通讯作者:
Chen, Jie
Chen, Jie
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang, Lei;Zhu, Dahai;Meng, Yunxiao;Zhang, Qiang;Chen, Jie

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E3泛素连接酶对蛋白质的泛素化在肿瘤的发生发展中起着重要作用。在这项研究中,我们提供了实验证据,证明含有RNF13的环指蛋白是ER/Golgi膜相关的E3泛素连接酶,其环指结构域是泛素连接酶活性所必需的。免疫组织化学检测72例胰腺导管腺癌及癌旁正常组织中有30例(41.7%,30/72)呈RNF13高表达,其表达与组织学分级显著相关(P=0.024)。此外,RNF13在慢性胰腺炎(CP)和胰腺上皮内瘤变(PanIN)癌前病变中的阳性表达分别为79.3%(23/29)和62.8%(22/35)。此外,PDAC组织中RNF13的表达与Tenascin-C的表达显著相关(P=0.004),进一步支持了RNF13在肿瘤进展中的作用。在胰腺癌细胞MiaPaca-2中过表达野生型而不是环状结构域突变的RNF13增加了基质金属蛋白酶-9的侵袭潜能和明胶溶解活性。综上所述,这些发现表明RNF13是一种新的E3泛素连接酶,参与胰腺癌的发生;泛素介导的RNF13对蛋白质的修饰可能参与胰腺癌的发生。
Protein ubiquitination by E3 ubiquitin ligases plays an important role in cancer development. In this study, we provide experimental evidence that a RING-finger-containing protein RNF13 is an ER/Golgi membrane-associated E3 ubiquitin ligase and its RING finger domain is required for the ubiquitin ligase activity. Immunohistochemical analysis of pancreatic ductal adenocarcinoma (PDAC) and paracancerous normal tissues from 72 patients documented RNF13 over-expression in 30 tumor samples (41.7%, 30/72), and its expression was significantly associated with histological grading (P= 0.024). In addition, RNF13 was detected in precancerous lesions: tubular complexes in chronic pancreatitis (CP) and pancreatic intraepithelial neoplasia (PanIN)(79.3%, 23/29 and 62.8%, 22/35, respectively). Moreover, RNF13 staining was significantly correlated with Tenascin-C expression (P= 0.004) in PDAC samples, further supporting the role of RNF13 in cancer progression. Over-expression of wild type but not RING domain-mutant RNF13 in pancreatic MiaPaca-2 cancer cells increased invasive potential and gelatinolytic activity by matrix metalloproteinase-9. Taken together, these findings reveal that RNF13 is a novel E3 ubiquitin ligase involved in pancreatic carcinogenesis; ubiquitin-mediated modification of proteins by RNF13 may participate in pancreatic cancer development.
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