title: Interaction between p12CDK2AP1 and a novel unnamed protein product inhibits cell proliferation by regulating the cell cycle.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.forename: Xiangming
authors.initials: X
authors.lastname: Yang
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Ni
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Moyi
authors.initials: M
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D019175:DNA Methylation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000589993:BC006130 protein, human; C096151:CDK2AP1 protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins