title: Pyruvate kinase M2 interacts with DNA damage-binding protein 2 and reduces cell survival upon UV irradiation.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Mingsong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address: jumei_xinhua@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Fengqing
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address: LeiLvxh@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
mesh_terms: D000107:Acetylation; D017209:Apoptosis / Q000528:radiation effects; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C091435:DDB1 protein, human; C117669:DDB2 protein, human
keywords: Cell survival; DDB2; PKM2; Tumorigenesis; UV