ArticleJournal of virology2011
Role of calpain in the formation of human papillomavirus type 16 E1^E4 amyloid fibers and reorganization of the keratin network.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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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
16 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular Insights into HPV-Driven Cervical Cancer: Oncoproteins, Immune Evasion, and Epigenetic Modifications.Microorganisms · 2025Review
- Modulation of cytokeratin and cytokine/chemokine expression following influenza virus infection of differentiated human tonsillar epithelial cells.Journal of virology · 2025Article
- HPV-associated oropharyngeal cancer: in search of surrogate biomarkers for early lesions.Oncogene · 2024Review
- High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis.Cancers · 2020Review
- Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology.Frontiers in oncology · 2019Review
- Article
- Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.Diagnostic pathology · 2017Article
- Potential Role of E4 Protein in Human Papillomavirus Screening: a ReviewAsian Pacific journal of cancer prevention : APJCP · 2017Review
- Review
- Investigating Diagnostic Problems of CIN1 and CIN2 Associated With High-risk HPV by Combining the Novel Molecular Biomarker PanHPVE4 With P16INK4a.The American journal of surgical pathology · 2015Article
- Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Article
- Human papillomavirus type 1 E1^E4 protein is a potent inhibitor of the serine-arginine (SR) protein kinase SRPK1 and inhibits phosphorylation of host SR proteins and of the viral transcription and replication regulator E2.Journal of virology · 2014Article
- The role of ubiquitin and ubiquitin-like modification systems in papillomavirus biology.Viruses · 2014Review
- Human papillomavirus infections: warts or cancer?Cold Spring Harbor perspectives in biology · 2013Review
- HPV-18 E6 mutants reveal p53 modulation of viral DNA amplification in organotypic cultures.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia.Obstetrics and gynecology international · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The human papillomavirus (HPV) type 16 E1^E4 (16E1^E4) protein is expressed in the middle to upper layers of infected epithelium and has several roles within the virus life cycle. It is apparent that within the epithelium there are multiple species of 16E1^E4 that differ in length and/or degree of phosphorylation and that some or all of these can associate with the cellular keratin networks, leading to network disruption. We show here that the cellular cysteine protease calpain cleaves the 16E1^E4 protein after amino acid 17 to generate species that lack the N terminus. These C-terminal fragments are able to multimerize and form amyloid-like fibers. This can lead to accumulation of 16E1^E4 and disruption of the normal dynamics of the keratin networks. The cleavage of E1^E4 proteins by calpain may be a common strategy used by α-group viruses, since we show that cleavage of type 18 E1^E4 in raft culture is also dependent on calpain. Interestingly, the cleavage of 16E1^E4 by calpain appears to be highly regulated as differentiation of HPV genome-containing cells by methylcellulose is insufficient to induce cleavage. We hypothesize that this is important since it ensures that the formation of the amyloid fibers is not prematurely triggered in the lower layers and is restricted to the upper layers, where calpain is active and where disruption of the keratin networks may aid virus release.
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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.