Role of the Multifunctional DNA Repair and Redox Signaling Protein Ape1/Ref-1 in Cancer and Endothelial Cells: Small-Molecule Inhibition of the Redox Function of Ape1
- 1 November 2008
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 10 (11), 1853-1867
- https://doi.org/10.1089/ars.2008.2120
Abstract
The DNA base excision-repair pathway is responsible for the repair of DNA damage caused by oxidation/alkylation and protects cells against the effects of endogenous and exogenous agents. Removal of the damaged base creates a baseless (AP) site. AP endonuclease1 (Ape1) acts on this site to continue the BER-pathway repair. Failure to repair baseless sites leads to DNA strand breaks and cytotoxicity. In addition to the repair role of Ape1, it also functions as a major redox-signaling factor to reduce and activate transcription factors such as AP1, p53, HIF-1α, and others that control the expression of genes important for cell survival and cancer promotion and progression. Thus, the Ape1 protein interacts with proteins involved in DNA repair, growth-signaling pathways, and pathways involved in tumor promotion and progression. Although knockdown studies with siRNA have been informative in studying the role of Ape1 in both normal and cancer cells, knocking down Ape1 does not reveal the individual role of the redox or repair functions of Ape1. The identification of small-molecule inhibitors of specific Ape1 functions is critical for mechanistic studies and translational applications. Here we discuss small-molecule inhibition of Ape1 redox and its effect on both cancer and endothelial cells. Antioxid. Redox Signal. 10, 1853–1867.Keywords
This publication has 78 references indexed in Scilit:
- Evolution of the redox function in mammalian apurinic/apyrimidinic endonucleaseMutation Research, 2008
- Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growthDNA Repair, 2008
- APE1/Ref-1 regulates PTEN expression mediated by Egr-1Free Radical Research, 2008
- Altering DNA base excision repair: Use of nuclear and mitochondrial‐targeted N‐methylpurine DNA glycosylase to sensitize astroglia to chemotherapeutic agentsGlia, 2007
- Targeting DNA repair as a promising approach in cancer therapyEuropean Journal Of Cancer, 2007
- Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediatesNucleic Acids Research, 2007
- XRCC1 interactions with base excision repair DNA intermediatesDNA Repair, 2007
- Human base excision repair complex is physically associated to DNA replication and cell cycle regulatory proteinsNucleic Acids Research, 2007
- The Interaction between Ku Antigen and REF1 Protein Mediates Negative Gene Regulation by Extracellular CalciumPublished by Elsevier ,1996
- Aphidicolin-sensitive DNA repair synthesis in human fibroblasts damaged with bleomycin is distinct from UV-induced repairCarcinogenesis: Integrative Cancer Research, 1990