Regulation of interferon regulatory factor 1 by protein inhibitor of activated STAT 3

Xu, Danyang (2020) Regulation of interferon regulatory factor 1 by protein inhibitor of activated STAT 3. Masters thesis, Memorial University of Newfoundland.

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Abstract

Oncolytic viruses exploit tumor-specific cellular changes for selective replication, inducing cancer cell death. Our previous research showed that Ras/mitogen-activated protein kinase kinase (MEK) downregulation of interferon regulatory factor 1 (IRF1) is a major mechanism underlying viral oncolysis. Protein inhibitor of activated STAT 3 (PIAS3) is known as the E3 ligase of IRF1 sumoylation. The objective of this study was to identify if, and how, PIAS3 modulates cellular sensitivity to oncolytic viruses via regulation of IRF1. By conducting co-immunoprecipitation, I found that IRF1 has no direct interaction with PIAS3 found within HT1080 cells. However, CRISPR knockdown of PIAS3 increases IRF1 expression as well as transcription of IRF1-responsive anti-viral genes. Furthermore, PIAS3 knockdown HT1080 cells were equally sensitive to viral infection as their parent HT1080 cells. Together, these results demonstrate that PIAS3 does not directly interact with IRF1 but regulates expression and transcriptional activity of IRF1. Moreover, as CRISPR knockdown of PIAS3 did not change cellular sensitivity to viral infection, IRF1 modulation via PIAS3 does not play very critical roles in host innate antiviral responses.

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