细胞生物学
生物
DNA复制
缺氧(环境)
病毒复制
重编程
真核细胞DNA复制
细胞
DNA
细胞培养
遗传学
化学
氧气
有机化学
作者
Rajnish Kumar Singh,Erle S. Robertson,Dipayan Bose,Zachary L. Lamplugh,Kunfeng Sun,Yan Yuan,Paul M. Lieberman,Jianxin You,Erle S. Robertson
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2021-07-19
卷期号:10
被引量:2
摘要
The cellular adaptive response to hypoxia, mediated by high HIF1α levels includes metabolic reprogramming, restricted DNA replication and cell division. In contrast to healthy cells, the genome of cancer cells, and Kaposi's sarcoma associated herpesvirus (KSHV) infected cells maintains replication in hypoxia. We show that KSHV infection, despite promoting expression of HIF1α in normoxia, can also restrict transcriptional activity, and promoted its degradation in hypoxia. KSHV-encoded vCyclin, expressed in hypoxia, mediated HIF1α cytosolic translocation, and its degradation through a non-canonical lysosomal pathway. Attenuation of HIF1α levels by vCyclin allowed cells to bypass the block to DNA replication and cell proliferation in hypoxia. These results demonstrated that KSHV utilizes a unique strategy to balance HIF1α levels to overcome replication arrest and induction of the oncogenic phenotype, which are dependent on the levels of oxygen in the microenvironment.
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