title: Reactive oxygen species increase HEPN1 expression via activation of the XBP1 transcription factor.
abstract: Hepatocellular carcinoma downregulated 1 (HEPN1), a cell growth arrest- and apoptosis-related gene, is suppressed in hepatocellular carcinoma (HCC). However, transcriptional control of HEPN1 has not been characterized. Here, we show that exposure to reactive oxygen species (ROS) leads to upregulation of the mRNA expression of HEPN1 in HCC cell lines. Mechanistically, ROS increase production of an alternately spliced form of X-box binding protein 1 (XBP1s) and XBP1s increases HEPN1 expression by binding to the HEPN1 promoter, thereby acting as a transcriptional activator. Finally, HEPN1 overexpression increases the expression of p53, p21, and Bax, all of which are ROS-upregulated proteins.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: keynome@naver.com.
authors.forename: Hyeon Seop
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: drjung@snu.ac.kr.
authors.forename: Guhung
authors.initials: G
authors.lastname: Jung
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008113:Liver Neoplasms / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000071717:X-Box Binding Protein 1; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C549604:HEPN1 protein, human; D011506:Proteins; D017382:Reactive Oxygen Species; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide
keywords: Alternative splicing; Apoptosis; Hepatocellular carcinoma; Hydrogen peroxide; p21; p53