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Article

Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle

  • Authors:
    • Lijun Liu
    • Xiangming Yang
    • Qianwei Ni
    • Zhifeng Xiao
    • Yannan Zhao
    • Jin Han
    • Moyi Sun
    • Bing Chen
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Oral and Maxillofacial Surgery, Urumqi General Hospital of Lanzhou Military Command, Urumqi, Xinjiang 830000, P.R. China, Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, P.R. China, State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, P.R. China
  • Pages: 156-162
    |
    Published online on: November 15, 2013
       https://doi.org/10.3892/mmr.2013.1801
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Abstract

Human p12CDK2AP1 protein is encoded by the cyclin‑dependent kinase 2‑associated protein 1 (CDK2AP1) gene. This protein suppresses cell growth, differentiation and angiogenesis in numerous types of carcinoma by interacting with certain cell cycle proteins, including CDK2 and DNA polymerase α/primase. p12CDK2AP1 exerts its functions predominantly through protein‑protein interactions. Therefore, the identification of other p12CDK2AP1‑interacting proteins may clarify its role in cell cycle regulation and carcinogenesis. The aim of this study was to identify additional p12CDK2AP1‑interacting proteins. A novel unnamed protein product (UPP, BC006130) was identified through using a yeast two‑hybrid system. The interaction of p12CDK2AP1 with the UPP was further verified by glutathione S-transferase pull‑down and co‑immunoprecipitation experiments in vitro. The qPCR results following overexpression and siRNA assays demonstrated that the expression levels of the UPP were mediated by the CDK2AP1 gene. Furthermore, overexpression of the UPP gene was shown to shorten the length of the G2/M phase of the cell cycle in normal and tumor cell lines in a flow cytometry assay. The results of human tumor xenografts experiments in Balb/c nude mice indicated that stable transfection with the UPP gene was able to inhibit tumor cell proliferation in vivo. Overall, this study identified and characterized a novel interactive protein of p12CDK2AP1, which may inhibit cell proliferation by mediating the cell cycle. It expands the understanding of the mechanisms of p12CDK2AP1 and its potential as a cancer therapeutic target.
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1 

Todd R, McBride J, Tsuji T, et al: Deleted in oral cancer-1 (doc-1), a novel oral tumor suppressor gene. FASEB J. 9:1362–1370. 1995.PubMed/NCBI

2 

Daigo Y, Suzuki K, Maruyama O, et al: Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer. Genes Chromosomes Cancer. 20:204–207. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Tsuji T, Duh FM, Latif F, et al: Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1. J Biol Chem. 273:6704–6709. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Kohno Y, Patel V, Kim Y, et al: Apoptosis, proliferation and p12(doc-1) profiles in normal, dysplastic and malignant squamous epithelium of the Syrian hamster cheek pouch model. Oral Oncol. 38:274–280. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Rosenblatt J, Gu Y and Morgan DO: Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A. Proc Natl Acad Sci USA. 89:2824–2828. 1992. View Article : Google Scholar : PubMed/NCBI

6 

Matsuo K, Shintani S, Tsuji T, et al: p12(DOC-1), a growth suppressor, associates with DNA polymerase alpha/primase. FASEB J. 14:1318–1324. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Zheng J, Xue H, Wang T, et al: miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion. J Cell Biochem. 112:872–880. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Deshpande AM, Dai YS, Kim Y, et al: Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem cell differentiation. J Biol Chem. 284:6043–6047. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Tsuji T, Ibaragi S, Shima K, et al: Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth. Cancer Res. 68:10377–10386. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Cwikla SJ, Tsuji T, McBride J, Wong DT and Todd R: doc-1-mediated apoptosis in malignant hamster oral keratinocytes. J Oral Maxillofac Surg. 58:406–414. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Tao K, Fang M, Alroy J and Sahagian GG: Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer. 8:2282008. View Article : Google Scholar : PubMed/NCBI

12 

Hiyoshi Y, Watanabe M, Hirashima K, et al: p12CDK2-AP1 is associated with tumor progression and a poor prognosis in esophageal squamous cell carcinoma. Oncol Rep. 22:35–39. 2009.PubMed/NCBI

13 

Choi MG, Sohn TS, Park SB, et al: Decreased expression of p12 is associated with more advanced tumor invasion in human gastric cancer tissues. Eur Surg Res. 42:223–229. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Shin J, Yuan Z, Sreeramoju P, et al: A del T poly T (8) mutation in the 3′ untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC). Surgery. 142:222–227. 2007.PubMed/NCBI

15 

Zolochevska O and Figueiredo ML: Cell-cycle regulators cdk2ap1 and bicalutamide suppress malignant biological interactions between prostate cancer and bone cells. Prostate. 71:353–367. 2011. View Article : Google Scholar

16 

Figueiredo ML, Kim Y, St John MA and Wong DT: p12CDK2-AP1 gene therapy strategy inhibits tumor growth in an in vivo mouse model of head and neck cancer. Clin Cancer Res. 11:3939–3948. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Kar G, Gursoy A and Keskin O: Human cancer protein-protein interaction network: a structural perspective. PLoS Comput Biol. 5:e10006012009. View Article : Google Scholar : PubMed/NCBI

18 

Buajeeb W, Zhang X, Ohyama H, et al: Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its homolog, p14(DOC-1R). Biochem Biophys Res Commun. 315:998–1003. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Shintani S, Ohyama H, Zhang X, et al: p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein. Mol Cell Biol. 20:6300–6307. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Bonetta L: Protein-protein interactions: Interactome under construction. Nature. 468:851–854. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Bock C, Reither S, Mikeska T, Paulsen M, Walter J and Lengauer T: BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics. 21:4067–4068. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Le Guezennec X, Vermeulen M, Brinkman AB, et al: MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol. 26:843–851. 2006.PubMed/NCBI

23 

Spruijt CG, Bartels SJ, Brinkman AB, et al: CDK2AP1/DOC-1 is a bona fide subunit of the Mi-2/NuRD complex. Mol Biosyst. 6:1700–1706. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Yochum GS and Ayer DE: Role for the mortality factors MORF4, MRGX, and MRG15 in transcriptional repression via associations with Pf1, mSin3A, and Transducin-Like Enhancer of Split. Mol Cell Biol. 22:7868–7876. 2002. View Article : Google Scholar

25 

Peng H, Shintani S, Kim Y and Wong DT: Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with disrupted transforming growth factor-beta-Smad signaling pathway. Neoplasia. 8:1028–1036. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Marques RB, Dits NF, Erkens-Schulze S, van Ijcken WF, van Weerden WM and Jenster G: Modulation of androgen receptor signaling in hormonal therapy-resistant prostate cancer cell lines. PLoS One. 6:e231442011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu L, Yang X, Ni Q, Xiao Z, Zhao Y, Han J, Sun M and Chen B: Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle. Mol Med Rep 9: 156-162, 2014.
APA
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J. ... Chen, B. (2014). Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle. Molecular Medicine Reports, 9, 156-162. https://doi.org/10.3892/mmr.2013.1801
MLA
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J., Sun, M., Chen, B."Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle". Molecular Medicine Reports 9.1 (2014): 156-162.
Chicago
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J., Sun, M., Chen, B."Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle". Molecular Medicine Reports 9, no. 1 (2014): 156-162. https://doi.org/10.3892/mmr.2013.1801
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Yang X, Ni Q, Xiao Z, Zhao Y, Han J, Sun M and Chen B: Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle. Mol Med Rep 9: 156-162, 2014.
APA
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J. ... Chen, B. (2014). Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle. Molecular Medicine Reports, 9, 156-162. https://doi.org/10.3892/mmr.2013.1801
MLA
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J., Sun, M., Chen, B."Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle". Molecular Medicine Reports 9.1 (2014): 156-162.
Chicago
Liu, L., Yang, X., Ni, Q., Xiao, Z., Zhao, Y., Han, J., Sun, M., Chen, B."Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle". Molecular Medicine Reports 9, no. 1 (2014): 156-162. https://doi.org/10.3892/mmr.2013.1801
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