KSHV-encoded vCyclin can modulate HIF1α levels to promote DNA replication in hypoxia.

Autor:	Kumar Singh R; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.; Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Pei Y; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Bose D; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Lamplugh ZL; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Sun K; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Yuan Y; Department of Microbiology, Levy Building, School of Dental Medicine, University of Pennsylvania, Philadelphia, United States., Lieberman P; Program in Gene Regulation, The Wistar Institute, Philadelphia, United States., You J; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Robertson ES; Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jul 19; Vol. 10. Date of Electronic Publication: 2021 Jul 19.
DOI:	10.7554/eLife.57436
Abstrakt:	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. Competing Interests: RK, YP, DB, ZL, KS, YY, PL, JY, ER No competing interests declared (© 2021, Kumar Singh et al.)
Databáze:	MEDLINE
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