Pyruvate kinase M2 interacts with DNA damage-binding protein 2 and reduces cell survival upon UV irradiation.
Pyruvate Kinase M2 (PKM2) is highly expressed in many solid tumors and associated with metabolism reprogramming and proliferation of tumors. Here, we report that PKM2 can bind to DNA Damage-Binding Protein 2 (DDB2), which is necessary for global nucleotide excision repair of UV induced DNA damage. The binding is promoted ... by UV irradiation and K433 acetylation of PKM2. Over expression of PKM2 facilitates phosphorylation of DDB2 and impairs DDB2-DDB1 binding. Furthermore, knocking down of PKM2 increases cell survival upon UV irradiation, while over expression of PKM2 reduces cell survival and over expression of DDB2-DDB1 reverts this effect. These results reveal a previously unknown regulation of PKM2 on DDB2 and provide a possible mechanism for UV induced tumorigenesis.
Mesh Terms:
Acetylation, Apoptosis, Binding Sites, Carrier Proteins, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Epithelial Cells, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Membrane Proteins, Mutation, Phosphorylation, Protein Binding, RNA, Small Interfering, Signal Transduction, Thyroid Hormones, Ultraviolet Rays
Acetylation, Apoptosis, Binding Sites, Carrier Proteins, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Epithelial Cells, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Membrane Proteins, Mutation, Phosphorylation, Protein Binding, RNA, Small Interfering, Signal Transduction, Thyroid Hormones, Ultraviolet Rays
Biochem. Biophys. Res. Commun.
Date: Nov. 13, 2015
PubMed ID: 26410533
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