title: Dynamic Regulation of APE1/Ref-1 as a Therapeutic Target Protein.
abstract: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that plays a central role in the cellular response to DNA damage and redox regulation against oxidative stress. APE1/Ref-1 functions in the DNA base excision repair pathway, the redox regulation of several transcription factors, and the control of intracellular redox status through the inhibition of reactive oxygen species (ROS) production. APE1/Ref-1 is predominantly localized in the nucleus; however, its subcellular localization is dynamically regulated and it may be found in the mitochondria or elsewhere in the cytoplasm. Studies have identified a nuclear localization signal and a mitochondrial target sequence in APE1/Ref-1, as well as the involvement of the nuclear export system, as determinants of APE1/Ref-1 subcellular distribution. Recently, it was shown that APE1/Ref-1 is secreted in response to hyperacetylation at specific lysine residues. Additionally, post-translational modifications such as phosphorylation, S-nitrosation, and ubiquitination appear to play a role in fine-tuning the activities and subcellular localization of APE1/Ref-1. In this review, we will introduce the multifunctional role of APE1/Ref-1 and its potential usefulness as a therapeutic target in cancer and cardiovascular disease.
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Sunga
authors.initials: S
authors.lastname: Choi
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Joo
authors.affiliation: Research Institute of Medical Sciences, Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
keywords: Biomarkers; DNA-(apurinic or apyrimidinic site) lyase; Oxidation-reduction; Protein processing, post-translational