Reactive oxygen species increase HEPN1 expression via activation of the XBP1 transcription factor

Hyeon Seop Kim; Guhung Jung

doi:10.1016/j.febslet.2014.10.011

Reactive oxygen species increase HEPN1 expression via activation of the XBP1 transcription factor

FEBS Lett. 2014 Nov 28;588(23):4413-21. doi: 10.1016/j.febslet.2014.10.011. Epub 2014 Oct 19.

Authors

Hyeon Seop Kim¹, Guhung Jung²

Affiliations

¹ Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: keynome@naver.com.
² Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: drjung@snu.ac.kr.

PMID: 25448679
DOI: 10.1016/j.febslet.2014.10.011

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.

Keywords: Alternative splicing; Apoptosis; Hepatocellular carcinoma; Hydrogen peroxide; p21; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Carcinoma, Hepatocellular / pathology*
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
DNA-Binding Proteins / biosynthesis
DNA-Binding Proteins / metabolism*
Humans
Hydrogen Peroxide / pharmacology
Liver Neoplasms / pathology*
Promoter Regions, Genetic / drug effects
Promoter Regions, Genetic / genetics*
Proteins / genetics*
Reactive Oxygen Species / pharmacology*
Regulatory Factor X Transcription Factors
Transcription Factors / biosynthesis
Transcription Factors / metabolism*
Transcriptional Activation / drug effects
Tumor Suppressor Protein p53 / metabolism
Up-Regulation / drug effects*
X-Box Binding Protein 1
bcl-2-Associated X Protein / metabolism

Substances

Cyclin-Dependent Kinase Inhibitor p21
DNA-Binding Proteins
HEPN1 protein, human
Proteins
Reactive Oxygen Species
Regulatory Factor X Transcription Factors
Transcription Factors
Tumor Suppressor Protein p53
X-Box Binding Protein 1
XBP1 protein, human
bcl-2-Associated X Protein
Hydrogen Peroxide