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_26
Snippet: Type I IFNs and viral and microbial infections induce the expression of ISG15. Further, its conjugation to target proteins plays essential roles in innate immune responses, such as anti-viral and anti-microbial functions. Recent studies indicate that ISG15 and its conjugating system, including UBE1L (E1), UBCH8 (E2), and EFP (E3), are also induced under DNA damage conditions and this induction is positively regulated by p53. Moreover, p53-mediate.....
Document: Type I IFNs and viral and microbial infections induce the expression of ISG15. Further, its conjugation to target proteins plays essential roles in innate immune responses, such as anti-viral and anti-microbial functions. Recent studies indicate that ISG15 and its conjugating system, including UBE1L (E1), UBCH8 (E2), and EFP (E3), are also induced under DNA damage conditions and this induction is positively regulated by p53. Moreover, p53-mediated increase in the levels of ISG15 and its conjugating system leads to ISGylation of ï„Np63ï¡ and PCNA as well as itself. ISGylation of p53 forms a positive feedback loop for its transcriptional activation, resulting in the expression of p53-downstream target genes for cell cycle arrest and apoptosis under DNA damage conditions. On the other hand, DNA damage-induced ISGylation of ï„Np63ï¡ negatively regulates its anti-apoptotic and mitogenic functions by caspase-2-mediated destabilization. In addition, reversible PCNA ISGylation relays a signaling pathway to turn off error-prone TLS after DNA lesion bypass for suppressing UV-induced mutagenesis as well as for resuming normal DNA replication. Thus, it appears clear that ISG15 and its conjugation to target proteins play a crucial function in the control of cellular responses to genotoxic stresses and in turn in suppression of DNA damage-mediated tumorigenesis.
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