RNF13: a novel RING-type ubiquitin ligase over-expressed in pancreatic cancer.
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.
Zhang
Qiang
Q
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Tsinghua University, 5 Dong Dan San Tiao, Beijing, China.
Meng
Yunxiao
Y
Zhang
Lei
L
Chen
Jie
J
Zhu
Dahai
D
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002278:Carcinoma in Situ / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D035683:MicroRNAs; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000201:enzymology / Q000473:pathology; D054829:RING Finger Domains; D020539:Sequence Analysis, Protein; D019063:Tenascin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
D006023:Glycoproteins; D035683:MicroRNAs; C533109:Mirn127 microRNA, mouse; D019063:Tenascin; C540080:RNF13 protein, human; D044767:Ubiquitin-Protein Ligases