Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell
Lijun Liu1, Xiangming Yang, Qianwei Ni
1Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
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.
Insights
Researchers identified a novel protein that interacts with human p12CDK2AP1 (cyclin-dependent kinase 2-associated protein 1). This interaction suppresses cell proliferation and may offer new cancer therapeutic targets.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- p12CDK2AP1 (cyclin-dependent kinase 2-associated protein 1) is a protein that suppresses cell growth, differentiation, and angiogenesis in various carcinomas.
- Its functions are primarily mediated through protein-protein interactions, highlighting the need to identify interacting partners to understand its role in cell cycle regulation and carcinogenesis.
Purpose of the Study:
- To identify novel proteins that interact with human p12CDK2AP1.
- To characterize the functional role of a newly identified interacting protein in cell cycle regulation and tumor growth.
Main Methods:
- Yeast two-hybrid system for initial protein interaction screening.
- Glutathione S-transferase pull-down and co-immunoprecipitation assays for in vitro interaction verification.
- Quantitative PCR (qPCR), cell cycle analysis via flow cytometry, and in vivo tumor xenograft models in Balb/c nude mice.
Main Results:
- A novel unnamed protein product (UPP, BC006130) was identified as a p12CDK2AP1-interacting protein.
- UPP expression levels are regulated by the CDK2AP1 gene, and UPP overexpression shortens the G2/M phase of the cell cycle.
- In vivo studies demonstrated that UPP gene transfection inhibits tumor cell proliferation.
Conclusions:
- A novel p12CDK2AP1-interacting protein (UPP) was identified and characterized.
- This novel protein may inhibit cell proliferation by mediating the cell cycle, expanding the understanding of p12CDK2AP1 mechanisms.
- The identified protein represents a potential cancer therapeutic target.
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Inhibition of CDK Activity
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Positive Regulator Molecules
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