KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia
KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia
Abstract 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 restricts transcriptional activity, and promoted its degradation in hypoxia. KSHV-encoded vCyclin, expressed in hypoxia, mediated HIF1a 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 the 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.
Sun Kunfeng、Singh Rajnish Kumar、Lieberman Paul、Lamplugh Zachary L、You Jianxin、Robertson Erle S、Pei Yonggang、Yuan Yan
Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of PennsylvaniaDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of PennsylvaniaProgram in Gene Regulation, The Wistar InstituteDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of PennsylvaniaDepartment of Microbiology, Perelman School of Medicine University of PennsylvaniaDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of PennsylvaniaDepartment of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of PennsylvaniaDepartment of Microbiology, Levy Building, School of Dental Medicine, University of Pennsylvania
基础医学分子生物学细胞生物学
Sun Kunfeng,Singh Rajnish Kumar,Lieberman Paul,Lamplugh Zachary L,You Jianxin,Robertson Erle S,Pei Yonggang,Yuan Yan.KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2020.08.12.248005.点此复制
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