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We found that RNF146 expression by liquiritigenin was mediated by estrogen receptor activation and contributed to cytoprotective effect of liquiritigenin. High-throughput screen using a luciferase construct harboring the RNF146 promoter identified liquiritigenin as an RNF146 inducer. In SH-SY5Y cells, RNF146 expression conferred resistance to toxic stimuli that lead to PARP1 activation. Here we report that RNF146 expression and RNF146 inducers can prevent cell death elicited by Parkinson’s disease (PD)-associated and PARP1-activating stimuli. RNF146 has been shown to be neuroprotective against PAR polymerase-1 (PARP1)-induced cell death during stroke. RNF146 is an E3 ubiquitin ligase that specifically recognizes and polyubiquitinates poly (ADP-ribose) (PAR)-conjugated substrates for proteasomal degradation. Received: ApAccepted: SeptemPublished: October 11, 2017

Yunjong Lee, email: Lee, email: Shin, email: luciferase screen, preconditioning, RNF146, AIMP2, PARP1-dependent cell death *These authors contributed equally to this work Troncoso 4, 5, Joo-Ho Shin 1, 6, *, Yun-Il Lee 7, 8, * and Yunjong Lee 1, *ġDivision of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Republic of KoreaĢNational Development Institute of Korean Medicine, Gyeongsan 38540, Republic of KoreaģCollege of Pharmacy, Chosun University, Gwangju 501-759, Republic of KoreaĤDepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USAĥDepartment of Pathology, Division of Neuropathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USAĦSingle Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-Do 440-746, Republic of KoreaħWell Aging Research Center, Daegu Geongbuk Institute of Science and Technology, Daegu 42988, South KoreaĨCompanion Diagnostics and Medical Technology Research Group, Daegu Geongbuk Institute of Science and Technology, Daegu 42988, South Korea Hyojung Kim 1, Sangwoo Ham 1, Joon Yeop Lee 2, Areum Jo 1, Gum Hwa Lee 3, Yun-Song Lee 1, MyoungLae Cho 2, Heung-Mook Shin 2, Donghoon Kim 4, Olga Pletnikova 5, Juan C.