Repairing enzyme APE has two terminals: C-terminal and N-terminal.
Now the role of APE repair enzyme is well characterized but its both terminal participate in cancer progression. So which one is dominating is rational to target for anticancer?
APE1 over-expression is important in some cancers, and your question involves APE1 functions in DNA repair and in signaling. The N-terminal Cys, which acts in signaling, may be important in cancer progression and maintenance. The DNA repair function is critical to genome integrity and its loss may act in cancer etiology and is also a potential cancer therapeutic target as it is critical for DNA repair and cell survival. In APE1, the N-terminal cysteine (Cys) that acts in signaling and transcription activation. However this Cys is part of a single folded domain with the DNA binding and repair functions, so these two components are close together in the native unmodified enzyme. APE1 forms a 4-layer structure with central pairs of beta-sheets packed on both sides by helices, i.e. APE1 an integrated single domain structure. The reactive Cys falls on a central strand of one beta sheet where it will impact the beta sheet to helix folding interactions and likely the DNA binding site at the end of the beta strands (for the structure and coordinate files see S.E. Tsutakawa et al., J Biol Chem. 2013 Mar 22;288(12):8445-55). In terms of three-dimensional protein structures, a domain is defined as a folding unit, a stable folded region (that can exist independently of the rest of the amino acid sequence), or a functional unit (e.g. Zn fingers or the Rossmann fold domains that bind DNA). In essence, domains are a structural unit with more interactions within itself than with the rest of the sequence, as seen for APE1. This independence of domains is important for genetic engineering because they can often be used as building blocks and swapped with other regions to create new combined activities. Given its single domain structure, the DNA repair functions of APE1 appear structurally linked to the cysteine signaling response functions with transcription and to some cancers. APE1 cysteine oxidation state also seems linked to its trafficking into mitochondria, which use most of the oxygen in the cell and is a major source of reactive oxygen species. This is an ongoing area of research, and ideas as to how to quantitatively and specifically define functional relationships among the DNA repair, signaling, trafficking, folding, and transcription activities of APE1 are valuable for going forward. It would be useful to have chemical knock-downs of each separate activity and test their impacts on various cancers.
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