Login Register Cart 0
Mini-Review Article

The Role of CDK20 Protein in Carcinogenesis

Author(s): Sowmya Chivukula and Vasavi Malkhed*

Volume 24, Issue 10, 2023

Published on: 20 July, 2023

Page: [790 - 796] Pages: 7

DOI: 10.2174/1389450124666230719102112

Price: $65

Abstract

Cancer is a complex disease that develops when abnormal cells divide uncontrollably as a consequence of unregulated cell cycle protein activity. Therefore, the cell cycle is crucial for maintaining homeostasis inside the cells during DNA replication and cell division. The presence of mutations within specific genes can disrupt the equilibrium within cells, ultimately leading to the growth of cancer. CDK20 (Cyclin-Dependent Kinase 20) is recently identified as a major controller of cell cycle checkpoints, which regulate cell growth and proliferation and perform a role in the development of many malignancies. CCRK (Cell-Cycle Related Kinase) has recently been renamed CDK20. Emerging studies proclaimed that the upregulation of CDK20 was identified in cancers of the ovary, brain, colon, stomach, liver, and lung. CDK20 was thought to have Cyclin-dependent activating kinase (CAK) activity for CDK2 when it is complexed with Cyclin H. Furthermore, recent studies revealed that CDK20 is involved in the Wnt, EZH2/NF-B, and KEAP1-NRF2 signaling pathways, all of which are interconnected to cancer formation and proliferation. In addition, the structure of CDK20 was predicted using ColabFold, a powerful software integrating AlphaFold's advanced AI system. The present review focuses on a systematic overview of the current knowledge on CDK20 derived from in vitro and in vivo studies and emphasizes its role in carcinogenesis. The validation comparison of the existing CDK20 AlphaFold structure with the ColabFold was found to be exceptionally fast and accurate in generating reliable models.

Keywords: CDK20, CCRK, malignancies, wnt pathway, EZH2/NF-B signaling pathway, KEAP1-NRF2 signaling pathway.

« Previous Next »
Graphical Abstract

[1]
Nouri Z, Fakhri S, Nouri K, Wallace CE, Farzaei MH, Bishayee A. Targeting multiple signaling pathways in cancer: The rutin therapeutic approach. Cancers 2020; 12(8): 2276.
[http://dx.doi.org/10.3390/cancers12082276] [PMID: 32823876]
[2]
Vijayaraghavan S, Moulder S, Keyomarsi K, Layman RM. Inhibiting cdk in cancer therapy: Current evidence and future directions. Target Oncol 2018; 13(1): 21-38.
[http://dx.doi.org/10.1007/s11523-017-0541-2] [PMID: 29218622]
[3]
Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 2015; 14(2): 130-46.
[http://dx.doi.org/10.1038/nrd4504] [PMID: 25633797]
[4]
Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: Structures of cdks, their cyclin activators, and cip and INK4 inhibitors. J Mol Biol 1999; 287(5): 821-8.
[http://dx.doi.org/10.1006/jmbi.1999.2640] [PMID: 10222191]
[5]
Łukasik P, Baranowska-Bosiacka I, Kulczycka K, Gutowska I. Inhibitors of cyclin-dependent kinases: Types and their mechanism of action. Int J Mol Sci 2021; 22(6): 2806.
[http://dx.doi.org/10.3390/ijms22062806] [PMID: 33802080]
[6]
Łukasik P, Załuski M, Gutowska I. Cyclin-dependent kinases (Cdk) and their role in diseases development–review. Int J Mol Sci 2021; 22(6): 2935.
[http://dx.doi.org/10.3390/ijms22062935] [PMID: 33805800]
[7]
Arellano M, Moreno S. Regulation of CDK/cyclin complexes during the cell cycle. Int J Biochem Cell Biol 1997; 29(4): 559-73.
[http://dx.doi.org/10.1016/S1357-2725(96)00178-1] [PMID: 9363633]
[8]
Cicenas J, Valius M. The CDK inhibitors in cancer research and therapy. J Cancer Res Clin Oncol 2011; 137(10): 1409-18.
[http://dx.doi.org/10.1007/s00432-011-1039-4] [PMID: 21877198]
[9]
Yuan K, Wang X, Dong H, Min W, Hao H, Yang P. Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs. Acta Pharm Sin B 2021; 11(1): 30-54.
[http://dx.doi.org/10.1016/j.apsb.2020.05.001] [PMID: 33532179]
[10]
Visconti R, Della Monica R, Grieco D. Cell cycle checkpoint in cancer: A therapeutically targetable double-edged sword. J Exp Clin Cancer Res 2016; 35(1): 153.
[http://dx.doi.org/10.1186/s13046-016-0433-9] [PMID: 27670139]
[11]
Malumbres M. Cyclin-dependent kinases. Genome Biol 2014; 15(6): 122.
[http://dx.doi.org/10.1186/gb4184]
[12]
Malumbres M, Harlow E, Hunt T, et al. Cyclin-dependent kinases: A family portrait. Nat Cell Biol 2009; 11(11): 1275-6.
[http://dx.doi.org/10.1038/ncb1109-1275] [PMID: 19884882]
[13]
Lai L, Shin GY, Qiu H. The role of cell cycle regulators in cell survival—dual functions of cyclin-dependent kinase 20 and p21cip1/waf1. Int J Mol Sci 2020; 21(22): 8504.
[http://dx.doi.org/10.3390/ijms21228504]
[14]
Tian Y, Wan H, Tan G. Cell cycle-related kinase in carcinogenesis. Oncol Lett 2012; 4(4): 601-6.
[http://dx.doi.org/10.3892/ol.2012.828] [PMID: 23205069]
[15]
Wu GQ, Xie D, Yang GF, et al. Cell cycle-related kinase supports ovarian carcinoma cell proliferation via regulation of cyclin d1 and is a predictor of outcome in patients with ovarian carcinoma. Int J Cancer 2009; 125(11): 2631-42.
[http://dx.doi.org/10.1002/ijc.24630] [PMID: 19672860]
[16]
Suryadevara R, Fadel H, Michelhaugh SK, et al. Tumors of the central nervous system. Nanotechnology-Based Target Drug Deliv Syst Brain Tumors 2018; 1-26.
[http://dx.doi.org/10.1016/B978-0-12-812218-1.00001-4]
[17]
Ng SSM, Cheung YT, An XM, et al. Cell cycle-related kinase: A novel candidate oncogene in human glioblastoma. J Natl Cancer Inst 2007; 99(12): 936-48.
[http://dx.doi.org/10.1093/jnci/djm011] [PMID: 17565152]
[18]
Liu Y, Wu C, Galaktionov K. p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells. J Biol Chem 2004; 279(6): 4507-14.
[http://dx.doi.org/10.1074/jbc.M309995200] [PMID: 14597612]
[19]
Caligiuri M, Becker F, Murthi K, et al. A proteome-wide CDK/CRK-specific kinase inhibitor promotes tumor cell death in the absence of cell cycle progression. Chem Biol 2005; 12(10): 1103-15.
[http://dx.doi.org/10.1016/j.chembiol.2005.08.008] [PMID: 16242653]
[20]
Kaldis P, Solomon MJ. Analysis of CAK activities from human cells. Eur J Biochem 2000; 267(13): 4213-21.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01455.x] [PMID: 10866826]
[21]
Yao H, Ashihara E, Strovel JW, et al. AV-65, a novel Wnt/β-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model. Blood Cancer J 2011; 1(11): e43.
[http://dx.doi.org/10.1038/bcj.2011.41] [PMID: 22829079]
[22]
Yang K, Wang X, Zhang H, et al. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: Implications in targeted cancer therapies. Lab Invest 2016; 96(2): 116-36.
[http://dx.doi.org/10.1038/labinvest.2015.144] [PMID: 26618721]
[23]
An X, Ng SS, Xie D, et al. Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis. Eur J Cancer 2010; 46(9): 1752-61.
[http://dx.doi.org/10.1016/j.ejca.2010.04.007] [PMID: 20466538]
[24]
Wang R, Xu X, Zhu H, et al. Androgen receptor promotes gastric carcinogenesis via upregulating cell cycle-related kinase expression. J Cancer 2019; 10(18): 4178-88.
[http://dx.doi.org/10.7150/jca.34430] [PMID: 31413736]
[25]
Low JT, Lin GL, Chan MWY. CCRK—a hub for liver metastasis and cancer. Cell Mol Immunol 2021; 18(5): 1341-2.
[http://dx.doi.org/10.1038/s41423-020-00569-5] [PMID: 33139906]
[26]
Feng H, Cheng ASL, Tsang DP, et al. Cell cycle–related kinase is a direct androgen receptor–regulated gene that drives β-catenin/T cell factor–dependent hepatocarcinogenesis. J Clin Invest 2011; 121(8): 3159-75.
[http://dx.doi.org/10.1172/JCI45967] [PMID: 21747169]
[27]
Wang Q, Ma J, Lu Y, et al. CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells. Oncogene 2017; 36(37): 5321-30.
[http://dx.doi.org/10.1038/onc.2017.161] [PMID: 28534518]
[28]
Xie Z, Hou S, Yang X, et al. Lessons learned from past cyclin-dependent kinase drug discovery efforts. J Med Chem 2022; 65(9): 6356-89.
[29]
Yu Z, Feng H, Sun X, et al. Bufalin suppresses hepatocarcinogenesis by targeting β-catenin/TCF signaling via cell cycle-related kinase. Sci Rep 2018; 8(1): 3891.
[http://dx.doi.org/10.1038/s41598-018-22113-2] [PMID: 29497076]
[30]
Varadi M, Anyango S, Deshpande M, et al. Alphafold protein structure database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res 2022; 50(D1): D439-44.
[http://dx.doi.org/10.1093/nar/gkab1061] [PMID: 34791371]
[31]
Tunyasuvunakool K, Adler J, Wu Z, et al. Highly accurate protein structure prediction for the human proteome. Nature 2021; 596(7873): 590-6.
[http://dx.doi.org/10.1038/s41586-021-03828-1] [PMID: 34293799]
[32]
Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: Making protein folding accessible to all. Nat Methods 2022; 19(6): 679-82.
[http://dx.doi.org/10.1038/s41592-022-01488-1] [PMID: 35637307]
[33]
Bateman A, Martin MJ, O’Donovan C, et al. UniProt: A hub for protein information. Nucleic Acids Res 2015; 43(D1): D204-12.
[http://dx.doi.org/10.1093/nar/gku989] [PMID: 25348405]
[34]
Gupta CLP, Gaur S, Soni MK. A Review on homology and thread modelling of protein sequenceusing protein similarity search and alphafold2 colab. J Pharm Negat Results 2022; 13: 1110-6.
[http://dx.doi.org/10.47750/pnr.2022.13.S08.140]
[35]
Feig M. Local protein structure refinement via molecular dynamics simulations with locPREFMD. J Chem Inf Model 2016; 56(7): 1304-12.
[http://dx.doi.org/10.1021/acs.jcim.6b00222] [PMID: 27380201]
[36]
Bowie JU, Lüthy R, Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. science 1991; 253(5016): 164-70.
[http://dx.doi.org/10.1126/science.1853201]
[37]
Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Cryst 1993; 26(2): 283-91.
[http://dx.doi.org/10.1107/S0021889892009944]
[38]
Wiederstein M, Sippl MJ. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007; 35(Web Server): W407-10.
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]

Rights & Permissions Print Cite
Article Metrics
59
2
© 2024 Bentham Science Publishers | Privacy Policy