ArticleJournal of virology2018
Human Cytomegalovirus Protein pUL38 Prevents Premature Cell Death by Binding to Ubiquitin-Specific Protease 24 and Regulating Iron Metabolism.
Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Ferritinophagy Rewires Carnitine-Dependent Lipid Metabolism to Inhibit PRRSV and IAV Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rotavirus infection induces ferroptosis through NCOA4-mediated ferritinophagy in IPEC-J2 cells.Journal of animal science and biotechnology · 2026Article
- Deferoxamine Inhibits Canine Parvovirus by Suppressing Ferroptosis and Viral Replication.Veterinary sciences · 2025Article
- Review
- The Protective Effects of Quercetin on Ferritinophagy in Alcoholic-Induced Liver Iron Overload.Current medical science · 2025Article
- Article
- Human cytomegalovirus RNA2.7 inhibits ferroptosis by upregulating ferritin and GSH via promoting ZNF395 degradation.PLoS pathogens · 2024Article
- USP24 promotes autophagy-dependent ferroptosis in hepatocellular carcinoma by reducing the K48-linked ubiquitination of Beclin1.Communications biology · 2024Article
- NCI677397 targeting USP24-mediated induction of lipid peroxidation induces ferroptosis in drug-resistant cancer cells.Molecular oncology · 2024Article
- The emerging role of nuclear receptor coactivator 4 in health and disease: a novel bridge between iron metabolism and immunity.Cell death discovery · 2024Review
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Targeting ferroptosis and ferritinophagy: new targets for cardiovascular diseases.Journal of Zhejiang University. Science. B · 2024Review
- CLPTM1L is a GPI-anchoring pathway component targeted by HCMV.The Journal of cell biology · 2023Article
- The role of autophagy in viral infections.Journal of biomedical science · 2023Review
- The role of ferroptosis in virus infections.Frontiers in microbiology · 2023Review
- Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases.Frontiers in microbiology · 2022Review
- Human Cytomegalovirus miR-UL70-3p Downregulates the HInternational journal of molecular sciences · 2021Article
- Herpesvirus Regulation of Selective Autophagy.Viruses · 2021Review
- Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases.International journal of molecular sciences · 2021Review
- Ciclopirox olamine induces ferritinophagy and reduces cyst burden in polycystic kidney disease.JCI insight · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) protein pUL38 has been shown to prevent premature cell death by antagonizing cellular stress responses; however, the underlying mechanism remains unknown. In this study, we identified the host protein ubiquitin-specific protease 24 (USP24) as an interaction partner of pUL38. Mutagenesis analysis of pUL38 revealed that amino acids TFV at positions 227 to 230 were critical for its interaction with USP24. Mutant pUL38 TFV/AAA protein did not bind to USP24 and failed to prevent cell death induced by pUL38-deficient HCMV infection. Knockdown of USP24 suppressed the cell death during pUL38-deficient HCMV infection, suggesting that pUL38 achieved its function by antagonizing the function of USP24. We investigated the cellular pathways regulated by USP24 that might be involved in the cell death phenotype by testing several small-molecule compounds known to have a protective effect during stress-induced cell death. The iron chelators ciclopirox olamine and Tiron specifically protected cells from pUL38-deficient HCMV infection-induced cell death, thus identifying deregulated iron homeostasis as a potential mechanism. Protein levels of nuclear receptor coactivator 4 (NCOA4) and lysosomal ferritin degradation, a process called ferritinophagy, were also regulated by pUL38 and USP24 during HCMV infection. Knockdown of USP24 decreased NCOA4 protein stability and ferritin heavy chain degradation in lysosomes. Blockage of ferritinophagy by genetic inhibition of NCOA4 or Atg5/Atg7 prevented pUL38-deficient HCMV infection-induced cell death. Overall, these results support the hypothesis that pUL38 binds to USP24 to reduce ferritinophagy, which may then protect cells from lysosome dysfunction-induced cell death.
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