title: Interactome Analysis Reveals a Novel Role for RAD6 in the Regulation of Proteasome Activity and Localization in Response to DNA Damage.
abstract: RAD6, an E2 ubiquitin-conjugating enzyme, is a key node for determining different DNA damage repair pathways, controlling both the error-prone and the error-free DNA damage repair pathways through differential regulation of the ubiquitination of the proliferating cell nuclear antigen (PCNA) protein. However, whether other pathways are involved in the RAD6-mediated regulation of DNA damage repair is still unclear. To deeply understand the molecular mechanisms of RAD6 in DNA damage repair, we performed a proteomic analysis and identified the changes of the protein-protein interaction (PPI) networks of RAD6 before and after X-ray irradiation. Furthermore, our study indicated that a proteasome-related event is likely involved in the DNA damage repair process. Moreover, we found that RAD6 promotes proteasome activity and nuclear translocation by enhancing the degradation of PSMF1 and the lamin B receptor (LBR). Therefore, we provide a novel pathway that is employed by RAD6 in response to DNA damage.
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Hongli
authors.initials: H
authors.lastname: An
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai, People's Republic of China.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, Shanghai, Shanghai, People's Republic of China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Gu
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: People's Hospital of Zunhua, School of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: People's Hospital of Zunhua, School of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, People's Republic of China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan, Republic of China.
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Lai
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai, People's Republic of China.
authors.forename: Ya-Bin
authors.initials: YB
authors.lastname: Li
authors.affiliation: Center for Translational Medicine at The First Affiliated Hospital, School of Forensic Sciences, School of Pharmacy, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, People's Republic of China chensu@xjtu.edu.cn sfl@tongji.edu.cn.|Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai, People's Republic of China.|People's Hospital of Zunhua, School of Life Sciences, North China University of Science and Technology, Tangshan, Hebei, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai, People's Republic of China chensu@xjtu.edu.cn sfl@tongji.edu.cn.
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Sun
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D057809:HEK293 Cells; D006801:Humans; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D060066:Protein Interaction Maps; D011506:Proteins / Q000378:metabolism; D059748:Proteolysis / Q000528:radiation effects; D040901:Proteomics / Q000379:methods*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D014965:X-Rays; D000097682:Lamin B Receptor
chemical_list: D046988:Proteasome Endopeptidase Complex; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D000097682:Lamin B Receptor; C121623:PSMF1 protein, human; C471545:UBE2A protein, human; C471546:UBE2B protein, human; C548045:proteasome activator PA700 subunit p58, human
keywords: DNA damage; LBR; PSMD3; PSMF1; RAD6; interactome analysis; proteasome