期刊
MOLECULAR CELL
卷 46, 期 1, 页码 79-90出版社
CELL PRESS
DOI: 10.1016/j.molcel.2012.02.004
关键词
-
资金
- National Institutes of Health (NIH) [AI067952, CA097093, R01GM069530, AI051686, P41 RR011823]
- Pioneer Developmental Chair from the Salk Institute
- predoctoral Ruth L. Kirschstein National Research Service (NIH/National Cancer Institute [NCI]) [T32 CA009523]
- Natural Sciences and Engineering Research Council of Canada
- American Cancer Society
- NCI [CA14195, CA80100]
- ALSAC
- St. Jude Cancer Center [NIH5P30CA021765]
- Howard Hughes Medical Institute
- MRC [MC_UP_A550_1030] Funding Source: UKRI
- Medical Research Council [MC_UP_A550_1030] Funding Source: researchfish
Viral hijacking of cellular processes relies on the ability to mimic the structure or function of cellular proteins. Many viruses encode ubiquitin ligases to facilitate infection, although the mechanisms by which they select their substrates are often unknown. The Herpes Simplex Virus type-1-encoded E3 ubiquitin ligase, ICP0, promotes infection through degradation of cellular proteins, including the DNA damage response E3 ligases RNF8 and RNF168. Here we describe a mechanism by which this viral E3 hijacks a cellular phosphorylation-based targeting strategy to degrade RNF8. By mimicking a cellular phosphosite, ICP0 binds RNF8 via the RNF8 forkhead associated (FHA) domain. Phosphorylation of ICP0 T67 by CK1 recruits RNF8 for degradation and thereby promotes viral transcription, replication, and progeny production. We demonstrate that this mechanism may constitute a broader viral strategy to target other cellular factors, highlighting the importance of this region of the ICP0 protein in countering intrinsic antiviral defenses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据