ArticleCell death & disease2021
Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Selinexor plus tislelizumab in patients with relapsed/refractory natural killer/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial.The oncologist · 2026Article
- Screening of the Pandemic Response Box Library Identified CRM1/XPO1 as an Anti-Mammarenavirus Druggable Target.Viruses · 2026Article
- Article
- Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modulation of anti-tumour immunity by XPO1 inhibitors.Exploration of targeted anti-tumor therapy · 2025Review
- IFIT3 mediates TBK1 phosphorylation to promote activation of pDCs and exacerbate systemic sclerosis in mice.Clinical and translational medicine · 2024Article
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.Autophagy · 2024Article
- Identifying novel inhibitors targeting Exportin-1 for the potential treatment of COVID-19.Archives of microbiology · 2024Article
- Novel-and Not So Novel-Inhibitors of the Multifunctional CRM1 Protein.Oncology reviews · 2024Review
- METTL16 controls Kaposi's sarcoma-associated herpesvirus replication by regulating S-adenosylmethionine cycle.Cell death & disease · 2023Article
- THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification.Cell death & disease · 2023Article
- Autophagy as a dual-faced host response to viral infections.Frontiers in cellular and infection microbiology · 2023Review
- Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management.Biomedicines · 2022Review
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- Activation and Evasion of Innate Immunity by Gammaherpesviruses.Journal of molecular biology · 2022Review
- Review
- HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response.Viruses · 2021Review
- Article
- The Second-Generation XPO1 Inhibitor Eltanexor Inhibits Human Cytomegalovirus (HCMV) Replication and Promotes Type I Interferon Response.Frontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nucleocytoplasmic transport of signaling modulators is essential for regulating cellular responses to extracellular stimulation and stress, as well as pathogen infection. Exportin 1 (XPO1), also known as chromosomal maintenance 1 (CRM1), mediates nuclear export of proteins, rRNAs, snRNAs, and some mRNAs. In this study, we have identified an essential role of XPO1 in regulating Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication during primary infection of primary human umbilical vein endothelial cells. Treatment with an XPO1 inhibitor KPT-8602 and short hairpin RNA (shRNA)-mediated knockdown of XPO1 reduced KSHV lytic replication but had no effect on KSHV entry and trafficking. XPO1 inhibition induced retention of autophagy adaptor protein p62 (SQSTM1) in the nucleus, which enhanced activation of TBK1 and IRF3. As a result, nuclear accumulation of p62 increased expression of innate immune-related genes including IRF7, ISG15, IFIT1, IFIT2, and IFIT3, leading to a reduction of KSHV lytic replication. These results illustrate a novel mechanism by which XPO1 mediates innate immune response and KSHV replication, and identify XPO1 as a potential therapeutic target and KPT-8602 as a promising therapeutic agent for KSHV infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.