![]() ![]() Human APE/Ref-1 is a multifunctional protein which possesses several completely different physiological activities. Data on the regulation of APE/Ref-1 degradation are not available so far. Depending on the cell type, APE/Ref-1 can be mainly localized in nucleus or cytoplasm or both. Deletion analysis showed that the C-terminal part of APE is important for the DNA binding and the AP-endonuclease activity of the protein, ( Synthesis and degradationĪPE/Ref-1 protein is expressed in a wide range of human cells. On SDS gels, recombinant APE has a molecular weight of 36.5 kDa. The human APE cDNA is about 1.4 kb in length and encompasses a coding region of 954 nucleotides, encoding a protein of 318 amino acids (Fig. The human APE gene (∼3 kb in size) is localized on chromosome 14 q11.2–12 and consists of four introns and five exons (Fig. This indicates that the diverse activities of APE/Ref-1 are regulated at the posttranslational level. Previously it was reported that phosphorylation of APE/Ref-1 by casein kinase II modulates the redox activity of the protein without influencing its DNA repair capacity. It is poorly investigated so far how these multiple physiological functions of APE/Ref-1 are regulated. Gene expression regulated by the trancription factors mentioned plays a central role in the cellular response to genotoxic stress, determining cellular survival and apoptosis. ![]() Recently, APE/Ref-1 was shown to regulate the transactivation and pro-apoptotic functions of p53. Independent of its characterization as DNA repair protein, APE was cloned as Redox-factor (Ref-1), that is important for the activation of transcription factors, such as activator protein 1 (AP1), p53 and nuclear factor kappaB (NF-κB), , by a redox-based mechanism. If unrepaired, AP sites block DNA replication and have both mutagenic and cytotoxic effects. ![]() In concert with several other DNA repair proteins, human apurinic/apyrimidinic endonuclease (APE) is part of the base excision repair machinery (BER) of eukaryotic cells. Modification of DNA bases can occur by endogenous mechanisms or as the consequence of exposure of cells to environmental chemical mutagens such as alkylating compounds. Apurinic/apyrimidinic (AP) sites in DNA are formed by spontaneous hydrolysis resulting in loss of purine or pyrimidine, exposure of cells to ionizing radiation and as products of N-glycosylases that act on modified DNA bases. ![]()
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