title: SENP1 deficiency promotes ER stress-induced apoptosis by increasing XBP1 SUMOylation.
abstract: The transcription factor X box-binding protein 1 (XBP1) is a key component of the endoplasmic reticulum (ER) stress response. Recently, it has been reported that the spliced XBP1 (XBP1s), an activated XBP1 during ER stress, can be SUMOylated. Here, we identify Sentrin/SUMO-specific protease 1 (SENP1) as a specific de-SUMOylation protease for XBP1. SENP1 can increase the transcriptional activity of XBP1. In Senp1 (-/-)  cells, the SUMOylated XBP1 is accumulated, and the expression of XBP1 target genes is downregulated in response to ER stress. Moreover, SENP1 deficiency significantly increases ER stress-induced apoptosis through accumulating XBP1 SUMOylation. These results reveal an essential function of SENP1 in ER stress response through regulating XBP1 SUMOylation.
authors.affiliation: Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Fan
authors.forename: Zhening
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Zou
authors.forename: Rong
authors.initials: R
authors.lastname: Cai
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zuo
authors.forename: Jinke
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D013312:Stress, Physiological; D058207:Sumoylation; D019284:Thapsigargin / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; D019284:Thapsigargin; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; C501974:Senp1 protein, mouse