ArticleBritish journal of cancer2011
The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed.
- New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.Molecular pharmacology · 2024Review
- ARHGEF16 expression correlates with proliferation, migration and invasion of colon cancer cells.Translational cancer research · 2023Article
- Role of IQGAP1 in Carcinogenesis.Cancers · 2021Review
- Article
- Double inhibition and activation mechanisms of Ephexin family RhoGEFs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.Nature biotechnology · 2021Article
- Review
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- Specificity in PDZ-peptide interaction networks: Computational analysis and review.Journal of structural biology: X · 2020Review
- Gene expression profiling informs HPV cervical histopathology but not recurrence/relapse after LEEP in ART-suppressed HIV+HPV+ women.Carcinogenesis · 2019Article
- Review
- Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network.International journal of cancer · 2018Article
- Detection of Small GTPase Prenylation and GTP Binding Using Membrane Fractionation and GTPase-linked Immunosorbent Assay.Journal of visualized experiments : JoVE · 2018Article
- GLI2 promotes cell proliferation and migration through transcriptional activation of ARHGEF16 in human glioma cells.Journal of experimental & clinical cancer research : CR · 2018Article
- The high-risk HPV E6 target scribble (hScrib) is required for HPV E6 expression in cervical tumour-derived cell lines.Papillomavirus research (Amsterdam, Netherlands) · 2016Article
- Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma.Oncotarget · 2015Article
- Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma.Medicina oral, patologia oral y cirugia bucal · 2015Article
- PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins.Biology · 2015Review
- Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI.PloS one · 2015Article
- Article
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Abstract
backgroundGuanidine exchange factor (GEF)-catalysed activation of Rho proteins such as Cdc42 has been shown to have a crucial role in cellular transformation, malignant progression and invasion. We have previously shown that the HPV16 E6 oncoprotein binds to the PDZ domain protein Tax-interacting-protein 1 (Tip-1) and we now report identification and functional analysis of a novel Tip-1 binding GEF.
methodsYeast two-hybrid, in vitro pull-down, site-directed mutagenesis, semiquantitative PCR, co-immunoprecipitation and western blotting were used to identify/confirm novel Tip-1 binding partners and analyse cellular expression levels. In vitro kinetic analyses of recombinant proteins, siRNA gene silencing and in cell assays were used to measure Rho protein activation.
resultsTax-interacting-protein 1 was shown to interact with ARHGEF16 by its carboxyl PDZ binding motif. Levels of ARHGEF16 were increased in transformed and immortalised cells expressing ectopic HPV16 E6 and Cdc42 was co-immunoprecipitated by ARHGEF16 in the presence of high-risk HPV E6. In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42 and this was increased by the addition of recombinant Tip-1 and E6. Cells expressing HPV16 E6 had higher levels of Cdc42 activation, which was decreased by siRNA silencing of either Tip-1 or ARHGEF16.
conclusionThese data suggest that HPV16 E6, Tip-1 and ARHGEF16 may cooperate to activate Cdc42 and support a potential link between the expression of HPV16 E6 and Cdc42 activation.
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