دورية أكاديمية
Inhibition of kinase IKKβ suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6.
| العنوان: | Inhibition of kinase IKKβ suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6. |
|---|---|
| المؤلفون: | Padash Barmchi M; Department of Biology, University of Oklahoma, Norman, OK, USA. mojgan.padash@ou.edu., Thomas M; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Thatte JV; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark., Vats A; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy., Zhang B; Division of Biological Sciences, University of Missouri, Columbia, MO, USA., Cagan RL; Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Glasgow, Scotland, UK., Banks L; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy. |
| المصدر: | Scientific reports [Sci Rep] 2021 Jan 13; Vol. 11 (1), pp. 1111. Date of Electronic Publication: 2021 Jan 13. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Compound Eye, Arthropod/*abnormalities , DNA-Binding Proteins/*metabolism , Drosophila Proteins/*antagonists & inhibitors , Drosophila Proteins/*metabolism , I-kappa B Kinase/*antagonists & inhibitors , I-kappa B Kinase/*metabolism , Oncogene Proteins, Viral/*metabolism , Uterine Cervical Neoplasms/*pathology, Animals ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Cell Transformation, Viral ; Compound Eye, Arthropod/cytology ; Compound Eye, Arthropod/growth & development ; Compound Eye, Arthropod/metabolism ; Drosophila ; Female ; Humans ; Nucleoside-Phosphate Kinase/metabolism ; PDZ Domains ; Phosphorylation ; Proteolysis ; Ubiquitin-Protein Ligases/metabolism |
| مستخلص: | Human papillomavirus (HPV) is the leading cause of cervical cancer and has been implicated in several other cancer types including vaginal, vulvar, penile, and oropharyngeal cancers. Despite the recent availability of a vaccine, there are still over 310,000 deaths each year worldwide. Current treatments for HPV-mediated cancers show limited efficacy, and would benefit from improved understanding of disease mechanisms. Recently, we developed a Drosophila 'HPV 18 E6' model that displayed loss of cellular morphology and polarity, junctional disorganization, and degradation of the major E6 target Magi; we further provided evidence that mechanisms underlying HPV E6-induced cellular abnormalities are conserved between humans and flies. Here, we report a functional genetic screen of the Drosophila kinome that identified IKK[Formula: see text]-a regulator of NF-κB-as an enhancer of E6-induced cellular defects. We demonstrate that inhibition of IKK[Formula: see text] reduces Magi degradation and that this effect correlates with hyperphosphorylation of E6. Further, the reduction in IKK[Formula: see text] suppressed the cellular transformation caused by the cooperative action of HPVE6 and the oncogenic Ras. Finally, we demonstrate that the interaction between IKK[Formula: see text] and E6 is conserved in human cells: inhibition of IKK[Formula: see text] blocked the growth of cervical cancer cells, suggesting that IKK[Formula: see text] may serve as a novel therapeutic target for HPV-mediated cancers. |
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| معلومات مُعتمدة: | U54 GM104938 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (Drosophila Proteins) 0 (E6 protein, Human papillomavirus type 18) 0 (Oncogene Proteins, Viral) EC 2.3.2.26 (UBE3A protein, human) EC 2.3.2.27 (Ubiquitin-Protein Ligases) EC 2.7.11.10 (I-kappa B Kinase) EC 2.7.11.10 (IKBKB protein, human) EC 2.7.11.10 (IKKbeta protein, Drosophila) EC 2.7.4.4 (Nucleoside-Phosphate Kinase) EC 2.7.4.8 (MAGI protein, Drosophila) |
| تواريخ الأحداث: | Date Created: 20210114 Date Completed: 20210806 Latest Revision: 20210806 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7807017 |
| DOI: | 10.1038/s41598-020-80193-5 |
| PMID: | 33441820 |
| قاعدة البيانات: | MEDLINE |
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