ArticleJournal of virology2010
The human papillomavirus type 18 E2 protein is a cell cycle-dependent target of the SCFSkp2 ubiquitin ligase.
Article in Journal of virology, 2010. 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, 38 citations in OpenAlex.
- Remodeling of Metabolic and Secretory Organelles During Oncogenic and Oncomodulatory Viral Infections.Viruses · 2026Review
- MCPyV small T antigen enhances HPV16 oncogene expression, promotes Ca Ski cell proliferation, and reduces 5-fluorouracil-induced apoptosis in cervical cancer cells.Infectious medicine · 2025Article
- Small-molecule compounds inhibiting S-phase kinase-associated protein 2: A review.Frontiers in pharmacology · 2023Review
- Review
- Like Brothers in Arms: How Hormonal Stimuli and Changes in the Metabolism Signaling Cooperate, Leading HPV Infection to Drive the Onset of Cervical Cancer.International journal of molecular sciences · 2022Review
- Identification of the Merkel Cell Polyomavirus Large Tumor Antigen Ubiquitin Conjugation Residue.International journal of molecular sciences · 2021Article
- Regulation of the Human Papillomavirus Lifecyle through Post-Translational Modifications of the Viral E2 Protein.Pathogens (Basel, Switzerland) · 2021Review
- Cyclic AMP-Dependent Protein Kinase Exhibits Antagonistic Effects on the Replication Efficiency of Different Human Papillomavirus Types.Journal of virology · 2021Article
- Review
- The Skp2 Pathway: A Critical Target for Cancer Therapy.Seminars in cancer biology · 2020Review
- Merkel Cell Polyomavirus Large T Antigen Unique Domain Regulates Its Own Protein Stability and Cell Growth.Viruses · 2020Article
- HPV-16 E2/E6 and POU5F1B as Biomarkers to Determine Cervical High-Grade Squamous Lesions and More.Journal of inflammation research · 2020Article
- Regulation of Cellular Metabolism by High-Risk Human Papillomaviruses.International journal of molecular sciences · 2018Review
- Full-length single-cell RNA-seq applied to a viral human cancer: applications to HPV expression and splicing analysis in HeLa S3 cells.GigaScience · 2015Article
- Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy.Cell cycle (Georgetown, Tex.) · 2015Article
- The role of ubiquitin and ubiquitin-like modification systems in papillomavirus biology.Viruses · 2014Review
- Brd4-mediated nuclear retention of the papillomavirus E2 protein contributes to its stabilization in host cells.Viruses · 2014Article
- The papillomavirus E2 proteins.Virology · 2013Review
- Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7.Cell host & microbe · 2013Article
- The Role of F-Box Proteins during Viral Infection.International journal of molecular sciences · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human papillomavirus type 18 (HPV-18) E2 gene is inactivated in cervical carcinoma after integration of the viral DNA into the host cellular genome. Since E2 represses the transcription of the two viral oncogenes E6 and E7, integration which allows their strong expression is considered a major step in transformation by HPV. We show here that E2 is specifically degraded at the end of the G(1) phase in a Brd4-independent manner, implying that its regulatory functions are cell cycle dependent. Degradation of E2 occurs via the Skp1/Cullin1/F-box Skp2 (SCF(Skp2)) ubiquitin ligase, since silencing of Skp2 induces stabilization of E2. In addition, the amino-terminal domain of E2 can interact with Skp2 as shown by coimmunoprecipitation experiments. We previously showed that E2 inhibits the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase, leading to accumulation of several of its substrates. We demonstrate here that Skp2, which is a known APC/C substrate in G(1), is also stabilized by E2. Therefore, by negative feedback, SCF(Skp2) activation could lead to E2 degradation and E6/E7 expression specifically in the late G(1) phase. Moreover, since the SCF(Skp2) can trigger S-phase entry and Skp2 itself is a known oncogene, we believe that E2-mediated accumulation of Skp2, together with E2 degradation leading to putative release of E6 and E7 inhibition, could induce premature S-phase entry in HPV-infected cells, pointing to a direct role of E2 in the early steps of HPV-mediated transformation.
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