ArticleProceedings of the National Academy of Sciences of the United States of America2010
Ubiquitination of lysine-331 by Kaposi's sarcoma-associated herpesvirus protein K5 targets HFE for lysosomal degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Metabolomic Analysis of Lytic KSHV Infection: Induced Host Nucleotide Metabolism Is Required for Infectious Virus Production.Viruses · 2026Article
- Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.Cell reports · 2020Article
- Pleiotropic roles of the ubiquitin-proteasome system during viral propagation.Life sciences · 2018Review
- Kaposi's sarcoma-associated herpesvirus K3 and K5 ubiquitin E3 ligases have stage-specific immune evasion roles during lytic replication.Journal of virology · 2014Article
- Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins down regulate both DC-SIGN and DC-SIGNR.PloS one · 2013Article
- Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.PLoS pathogens · 2013Article
- Construction and manipulation of a new Kaposi's sarcoma-associated herpesvirus bacterial artificial chromosome clone.Journal of virology · 2012Article
- Structural requirements for recognition of major histocompatibility complex class II by membrane-associated RING-CH (MARCH) protein E3 ligases.The Journal of biological chemistry · 2012Article
- The Ubiquitin System and Kaposi's Sarcoma-Associated Herpesvirus.Frontiers in microbiology · 2012Article
- What has the study of the K3 and K5 viral ubiquitin E3 ligases taught us about ubiquitin-mediated receptor regulation?Viruses · 2011Review
- Viral takeover of the host ubiquitin system.Frontiers in microbiology · 2011Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The nonclassical MHC class I-related (MHC-I) molecule HFE controls cellular iron homeostasis by a mechanism that has not been fully elucidated. We examined the regulation of HFE by K5, the E3 ubiquitin ligase encoded by Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), that is known to down-regulate classical MHC-I. K5 down-regulated HFE efficiently, using polyubiquitination of the membrane proximal lysine in the HFE cytoplasmic tail (K331), to target the molecule for degradation via ESCRT1/TSG101-dependent sorting from endosomes to multivesicular bodies (MVBs)/lysosomes. In the primary effusion lymphoma cell line BC-3, which carries latent KSHV, HFE was degraded rapidly upon virus reactivation. HFE was ubiquitinated on lysine-331 in unactivated BC-3 cells, conditions where K5 was not detectable, consistent with an endogenous E3 ubiquitin ligase controlling HFE expression. The results show regulated expression of HFE by ubiquitination, consistent with a role in cellular iron homeostasis, a molecular mechanism targeted by KSHV to achieve a positive iron balance.
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