Author: Jeon, Young Joo; Park, Jong Ho; Chung, Chin Ha
Title: Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress Document date: 2017_2_28
ID: w731ehtz_12
Snippet: Recently, we have shown that p53RE is present not only in the ISG15 gene but also in the promoter regions of the genes encoding UBE1L (E1), UBCH8 (E2), and EFP (E3), all of which are henceforth referred to as the ISG15-conjugating system (Park et al., 2016) . Accordingly, treatment with DNA-damaging agents, such as UV, camptothecin, and doxorubicin, markedly induces both the mRNA and protein further accelerates p53 ISGylation and subsequent proce.....
Document: Recently, we have shown that p53RE is present not only in the ISG15 gene but also in the promoter regions of the genes encoding UBE1L (E1), UBCH8 (E2), and EFP (E3), all of which are henceforth referred to as the ISG15-conjugating system (Park et al., 2016) . Accordingly, treatment with DNA-damaging agents, such as UV, camptothecin, and doxorubicin, markedly induces both the mRNA and protein further accelerates p53 ISGylation and subsequent processes for suppression of cell growth and tumor development by forming a positive feedback loop. When this loop is no longer necessary, UBP43 is induced and deISGylates p53 for destabilization. levels of UBE1L, UBCH8, and EFP in p53 +/+ cells, but not in p53 -/cells, and this induction can be abrogated by caffeine, an inhibitor of ATM/ATR kinases (Sarkaria et al., 1999) , which phosphorylate Chk1 and p53 for the expression of p53. In addition, DNA damage-mediated induction of the ISG15conjugating system is independent of type I IFNs, indicating that p53 alone can positively regulate the expression of ISG15 and its conjugation system.
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