Chonnam Med J.  2016 May;52(2):75-80. 10.4068/cmj.2016.52.2.75.

Dynamic Regulation of APE1/Ref-1 as a Therapeutic Target Protein

• Choi S
• Joo HK
• Jeon BH

• KMID: 2164316
• DOI: http://doi.org/10.4068/cmj.2016.52.2.75

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.

Keyword

DNA-(apurinic or apyrimidinic site) lyase; Protein processing, post-translational; Oxidation-reduction; Biomarkers

MeSH Terms

Active Transport, Cell Nucleus
Biomarkers
Cardiovascular Diseases
Cytoplasm
DNA
DNA Damage
DNA Repair
DNA-(Apurinic or Apyrimidinic Site) Lyase
Lysine
Mitochondria
Nuclear Localization Signals
Oxidation-Reduction
Oxidative Stress
Phosphorylation
Protein Processing, Post-Translational
Reactive Oxygen Species
Transcription Factors
Ubiquitin
Ubiquitination
Biomarkers
DNA
DNA-(Apurinic or Apyrimidinic Site) Lyase
Lysine
Nuclear Localization Signals
Reactive Oxygen Species
Transcription Factors
Ubiquitin

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