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

Liu,Lijun; Yang,Xiangming; Ni,Qianwei; Xiao,Zhifeng; Zhao,Yannan; Han,Jin; Sun,Moyi; Chen,Bing

doi:10.3892/mmr.2013.1801

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
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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
Published online on: November 15, 2013 https://doi.org/10.3892/mmr.2013.1801
Pages: 156-162

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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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