title: Inhibition of p53 deSUMOylation exacerbates puromycin aminonucleoside-induced apoptosis in podocytes.
abstract: Apoptosis is a major cause of reduced podocyte numbers, which leads to proteinuria and/or glomerulosclerosis. Emerging evidence has indicated that deSUMOylation, a dynamic post-translational modification that reverses SUMOylation, is involved in the apoptosis of Burkitt's lymphoma cells and cardiomyocytes; however, the impact of deSUMOylation on podocyte apoptosis remains unexplored. The p53 protein plays a major role in the pathogenesis of podocyte apoptosis, and p53 can be SUMOylated. Therefore, in the present study, we evaluated the effect of p53 deSUMOylation, which is regulated by sentrin/SUMO-specific protease 1 (SENP1), on podocyte apoptosis. Our results showed that SENP1 deficiency significantly increases puromycin aminonucleoside (PAN)-induced podocyte apoptosis. Moreover, SENP1 knockdown results in the accumulation of SUMOylated p53 protein and the increased expression of the p53 target pro-apoptotic genes, BAX, Noxa and PUMA, in podocytes during PAN stimulation. Thus, SENP1 may be essential for preventing podocyte apoptosis, at least partly through regulating the functions of p53 protein via deSUMOylation. The regulation of deSUMOylation may provide a novel strategy for the treatment of glomerular disorders that involve podocyte apoptosis.
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. wanglingyu0622@163.com.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. zjwssss2011@163.com.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. fangming0411@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. dlzhangtuaner@163.com.
authors.forename: Tuaner
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. wlciq007@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. pyran78@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. sn106@hotmail.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. dahuihui800@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Disease, PLA General Hospital, Beijing 100853, China. fubo_01@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Nephrology, Liaoning Translational Medicine Center of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. hllin@dlmedu.edu.cn.
authors.forename: Hongli
authors.initials: H
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011692:Puromycin Aminonucleoside / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494827:Bax protein, mouse; C488588:PUMA protein, mouse; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D011692:Puromycin Aminonucleoside; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C501974:Senp1 protein, mouse