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- W2065449346 abstract "The mammalian AP-endonuclease (APE1/Ref-1) plays a central role in the repair of oxidized and alkylated bases in mammalian genomes via the base excision repair (BER) pathway. However, APE1, unlike its E. coli prototype Xth, has two unique and apparently distinct transcriptional regulatory activities. APE1 functions as a redox effector factor (Ref-1) for several transcription factors including AP-1, HIF1-α, and p53. APE1 was also identified as a direct trans-acting factor for repressing human parathyroid hormone (PTH) and renin genes by binding to the negative calcium-response element (nCaRE) in their promoters. We have characterized APE1's post-translational modification, namely, acetylation which modulates its transcriptional regulatory function. Furthermore, stable interaction of APE1 with several other trans-acting factors including HIF-1α, STAT3, YB-1, HDAC1, and CBP/p300 and formation of distinct trans-acting complexes support APE1's direct regulatory function for diverse genes. Multiple functions of mammalian APE1, both in DNA repair and gene regulation, warrant extensive analysis of its own regulation and dissection of the mechanisms. In this review, we have discussed APE1's own regulation and its role as a transcriptional coactivator or corepressor by both re-dox-dependent and redox-independent (acetylation-mediated) mechanisms, and explore the potential utility of targeting these functions for enhancing drug sensitivity of cancer cells. Antioxid. Redox Signal. 11, 621–637." @default.
- W2065449346 created "2016-06-24" @default.
- W2065449346 creator A5008625683 @default.
- W2065449346 creator A5082029120 @default.
- W2065449346 creator A5091201451 @default.
- W2065449346 date "2009-03-01" @default.
- W2065449346 modified "2023-10-18" @default.
- W2065449346 title "Transcriptional Regulatory Functions of Mammalian AP-Endonuclease (APE1/Ref-1), an Essential Multifunctional Protein" @default.
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