Nm23-H1 Protein Binds to APE1 at AP Sites and Stimulates AP Endonuclease Activity Following Ionizing Radiation of the Human Lung Cancer A549 Cells |
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Authors: | Zhi-Min Zhang Xue-Qin Yang Dong Wang Ge Wang Zhen-Zhou Yang Yi Qing Zhi-Xiang Yang Meng-Xia Li De-Bing Xiang |
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Institution: | (1) Cancer Center, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, China; |
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Abstract: | Non-metastatic protein-23 homolog-1 (Nm23-H1) is a multifunctional protein with DNase and histidine protein kinase activities.
Human apurinic endonuclease-1 (APE1) is the AP endonuclease DNA base excision repair (BER) enzyme involved in several important
cellular functions. Since the relationship between Nm23-H1 and APE1 proteins is unclear, we evaluated their interaction at
different time points after irradiating human lung cancer A549 cells with X-rays. We found that Nm23-H1 and APE1 overexpression
was induced by irradiation in a dose- and time-dependent manner. Subcellular distribution pattern of both proteins was reversed
after irradiation. After irradiation, APE1 that initially showed nuclear localization was gradually increased in the cytoplasm,
whereas Nm23-H1 that mainly showed cytoplasmic localization was gradually increased in the nuclei of A549 cells. Nm23-H1 and
APE1 interaction was demonstrated by His-pull-down and co-immunoprecipitation assays. The presence of Nm23-H1/APE1 complex
in X-ray-irradiated A549 cells was also detected by DNA affinity precipitation analysis of a DNA fragment containing an AP
site. Although the AP endonuclease activity of Nm23-H1 was too weak to be detected, the AP endonuclease activity of APE1 was
increased with the enhanced Nm23-H1 expression. In conclusion, our data point to a mechanism by which Nm23-H1 protects cells
against oxidative stress through the engagement of DNA BER enzyme APE1. |
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