Keywords
Digestive tract
Gastrointestinal cancers
Submitted : 2021-08-31
Accepted : 2021-09-15
Published : 2021-09-30
Abstract
Ubiquitin-conjugating enzyme UBE2C is one of the important members of ubiquitin-proteasome pathway (UPP). Amplification and/or overexpression of UBE2C have been reported in many malignancies, and a high expression of UBE2C is associated with poor clinical outcomes. In this review, the pathological role of dysregulated UBE2C in gastrointestinal cancers and its potential role as a diagnostic and/or a prognostic marker as well as a therapeutic target in these cancers are discussed.
References
Ohtake F, Tsuchiya H, 2016, The Emerging Complexity of Ubiquitin Architecture. Journal of Biochemistry, 161(2): 125-133.
Yau R, Rape M, 2016, The Increasing Complexity of the Ubiquitin Code. Nature Cell Biology, 18(6): 579-586.
Handley PM, Mueckler M, Siegel NR, et al., 1991, Molecular Cloning, Sequence, and Tissue Distribution of the Human Ubiquitin-Activating Enzyme E1. Proceedings of the National Academy of Sciences of the United States of America, 88(1): 258-262.
Jin J, Li X, Gygi SP, et al., 2007, Dual E1 Activation Systems for Ubiquitin Differentially Regulate E2 Enzyme Charging. Nature, 447(7148): 1135-1138.
Michelle C, Vourc’h P, Mignon L, et al., 2009, What Was the Set of Ubiquitin and Ubiquitin-Like Conjugating Enzymes in the Eukaryote Common Ancestor? Journal of Molecular Evolution, 68(6): 616-628.
Li W, Bengtson MH, Ulbrich A, et al., 2008, Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle’s Dynamics and Signaling. Plos One, 3(1): e1487.
Burroughs AM, Jaffee M, Iyer LM, et al., 2008, Anatomy of the E2 Ligase Fold: Implications for Enzymology and Evolution of Ubiquitin/Ub-Like Protein Conjugation. Journal of Structural Biology, 162(2): 205-218.
Van Wijk SJ, Timmers HT, 2010, The Family of Ubiquitin-Conjugating Enzymes (E2s): Deciding Between Life and Death of Proteins. The FASEB Journal, 24(4): 981-993.
Winn PJ, Religa TL, Battey JND, et al., 2004, Determinants of Functionality in the Ubiquitin Conjugating Enzyme Family. Structure (Cambridge), 12(9): 1563-1574.
Summers MK, Pan B, Mukhyala K, et al., 2008, The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC. Molecular Cell, 31(4): 544-556.
Reddy SK, Rape M, Margansky WA, et al., 2007, Ubiquitination by the Anaphase-Promoting Complex Drives Spindle Checkpoint Inactivation. Nature, 446(7138): 921-925.
Van Ree JH, Jeganathan KB, Malureanu L, et al., 2010, Overexpression of the E2 Ubiquitin-Conjugating Enzyme UbcH10 Causes Chromosome Missegregation and Tumor Formation. The Journal of Cell Biology, 188(1): 83-100.
Townsley FM, Aristarkhov A , Beck S, et al., 1997, Dominant-Negative Cyclin-Selective Ubiquitin Carrier Protein E2-C/UbcH10 Blocks Cells in Metaphase. Proceedings of the National Academy of Sciences of the United States of America, 94(6): 2362-2367.
Jiang F, Basavappa R, 1999, Crystal Structure of the Cyclin-Specific Ubiquitin-Conjugating Enzyme from Clam, E2-C, at 2.0 A Resolution. Biochemistry, 38(38): 6471-6478.
Yanagida M, 2005, Basic Mechanism of Eukaryotic Chromosome Segregation. Philosophical Transactions Biological Sciences, 360(1455): 609-621.
Williamson A, Banerjee S, Zhu X, et al., 2011, Regulation of Ubiquitin Chain Initiation to Control the Timing of Substrate Degradation. Molecular Cell, 42(6): 744-757.
Hao Z, Zhang H, Cowell J, 2012, Ubiquitin-Conjugating Enzyme UBE2C: Molecular Biology, Role in Tumorigenesis, and Potential as a Biomarker. Tumor Biology, 33(3): 723-730.
Okamoto Y, Ozaki T, Miyazaki K, et al., 2003, UbcH10 is the Cancer-Related E2 Ubiquitin-Conjugating Enzyme. Cancer Research, 63(14): 4167-4173.
Pallante P, Berlingieri MT, Troncone G, et al., 2005, UbcH10 Overexpression May Represent a Marker of Anaplastic Thyroid Carcinomas. British Journal of Cancer, 93(4): 464.
Rawat A, Gopal G, Selvaluxmy G, et al., 2013, Inhibition of Ubiquitin Conjugating Enzyme UBE2C Reduces Proliferation and Sensitizes Breast Cancer Cells to Radiation, Doxorubicin, Tamoxifen and Letrozole. Cellular oncology, 36(6): 459-467.
Patel D, McCance DJ, 2010, Compromised Spindle Assembly Checkpoint Due to Altered Expression of UbcH10 and Cdc20 in Human Papillomavirus Type 16 E6- and E7-Expressing Keratinocytes. Journal of Virology, 84(21): 10956-10964.
Cheng J, Kang X, Zhang S, et al., 2007, SUMO-Specific Protease 1 is Essential for Stabilization of HIF1? during Hypoxia. Cell, 131(3): 584-595.
Yang M, Qu Y, Shi R, et al., 2016, Ubiquitin-Conjugating Enzyme Ubch10 Promotes Gastric Cancer Growth and is a Potential Biomarker for Gastric Cancer. Oncology Reports, 36(2): 779-786.
Bajaj S, Alam SK, Roy KS, et al., 2016, E2-Ubiquitin Conjugating Enzyme, UBE2C, is Reciprocally Regulated by Wild-Type and Gain-Of-Function Mutant p53. Journal of Biological Chemistry, 291(27): 14231-14247.
Cacciola NA, Calabrese C, Malapelle U, et al., 2016, UbcH10 Expression Can Predict Prognosis and Sensitivity to the Antineoplastic Treatment for Colorectal Cancer Patients. Molecular Carcinogenesis, 55(5): 793-807.
Bavi P, Uddin S, Ahmed M, et al., 2011, Bortezomib Stabilizes Mitotic Cyclins and Prevents Cell Cycle Progression Via Inhibition of UBE2C in Colorectal Carcinoma. The American Journal of Pathology, 178(5): 2109-2120.
Li SZ, Song Y, Zhang HH, et al., 2014, UbcH10 Overexpression Increases Carcinogenesis and Blocks ALLN Susceptibility in Colorectal Cancer. Scientific Reports, 4: 6910.
Sabitha K, Rajkumar T, 2012, Identification of Small Molecule Inhibitors Against UBE2C by Using Docking Studies. Bioinformation, 8(21): 1047.
Wang ST, Li DZ, Li JM, et al., 2015, Lentivirus-Mediated RNA Interference Targeting UbcH10 Reduces Cell Growth and Invasion of Human Osteosarcoma Cells Via Inhibition of Ki-67 and Matrix Metalloproteinases. Oncology Letters, 9(5): 2171-2176.
Pallante P, Malapelle U, Berlingieri MT, et al., 2013, UbcH10 Overexpression in Human Lung Carcinomas and Its Correlation with EGFR and p53 Mutational Status. European Journal of Cancer, 49(5): 1117-1126.
Lin J, Raoof DA, Wang Z, et al., 2006, Expression and Effect of Inhibition of the Ubiquitin-Conjugating Enzyme E2C on Esophageal Adenocarcinoma. Neoplasia, 8(12): 1062-1071.
Fujita T, Ikeda H, Taira N, et al., 2009, Overexpression of UbcH10 Alternates the Cell Cycle Profile and Accelerate the Tumor Proliferation in Colon Cancer. BMC Cancer, 9(1): 87.
Chen S, Chen Y, Hu C, et al., 2010, Association of Clinicopathological Features with UbcH10 Expression in Colorectal Cancer. Journal of Cancer Research and Clinical Oncology, 136(3): 419-426.
Han SS, Liu QG, Yao YM, et al., 2011, UbcH10 Expression in Hepatocellular Carcinoma and Its Clinicopathological Significance. Nan Fang Yi Ke Da Xue Xue Bao (Journal of Southern Medical University), 31(2): 280-284.
Zhao ZK, Wu WG, Chen L, et al., 2013, Expression of UbcH10 in Pancreatic Ductal Adenocarcinoma and Its Correlation with Prognosis. Tumor Biology, 34(3): 1473-1477.
Matsumoto A, Ishibashi Y, Urashima M, et al., 2014, High UbcH10 Protein Expression as a Marker of Poor Prognosis in Esophageal Squamous Cell Carcinoma. Anticancer Research, 34(2): 955-961.
Zhang HQ, Zhao G, Ke B, et al., 2018, Overexpression of UBE2C Correlates with Poor Prognosis in Gastric Cancer Patients. European Review for Medical and Pharmacological Sciences, 22(6): 1665-1671.