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Human DNA-PK Activates a STING-independent DNA Sensing Pathway
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Human DNA-PK Activates a STING-independent DNA Sensing Pathway. |
| 개인저자 | Burleigh, Katelyn. |
| 단체저자명 | University of Washington. Molecular and Cellular Biology. |
| 발행사항 | [S.l.]: University of Washington., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 65 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781085732963 |
| 학위논문주기 | Thesis (Ph.D.)--University of Washington, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Stetson, Daniel B. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Recognition of foreign nucleic acids is critical for antiviral defense. Detection of DNA is mediated by the cGAS-STING pathway, which activates a potent type I interferon response. This pathway is broadly required for antiviral defense across cell types and species, and its relevance in context of infection, cancer, and autoimmunity has been thoroughly established. However, we have discovered an additional STING-independent DNA sensing pathway (SIDSP) in human cells. Using STING KO human cell lines, we find that the induction of interferon is indeed abrogated at early timepoints, but surprisingly, at later timepoints, we observe a robust DNA-induced interferon response. Here we identify DNA-PK as the sensor for the SIDSP and demonstrate that its kinase activity is required for the antiviral response. We show that a heat shock protein HSPA8/HSC70 is phosphorylated after DNA stimulation and acts as a marker for the SIDSP. Finally, we explore how DNA viruses antagonize both the cGAS-STING pathway and the SIDSP. Our work highlights the importance of nucleic acid sensing for both host and virus and has implications for modulating DNA sensing in order to improve therapies for cancer or autoimmunity. |
| 일반주제명 | Immunology. Cellular biology. |
| 언어 | 영어 |
| 바로가기 | 
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