دورية أكاديمية
Molecular dissection of the E6 PBM identifies essential residues regulating Chk1 phosphorylation and subsequent 14-3-3 recognition.
| العنوان: | Molecular dissection of the E6 PBM identifies essential residues regulating Chk1 phosphorylation and subsequent 14-3-3 recognition. |
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| المؤلفون: | Vats A; International Centre for Genetic Engineering and Biotechnology, Padriciano, 99-34149, Trieste, Italy. Electronic address: aarushi.sharma2009@gmail.com., Thatte JV; International Centre for Genetic Engineering and Biotechnology, Padriciano, 99-34149, Trieste, Italy., Banks L; International Centre for Genetic Engineering and Biotechnology, Padriciano, 99-34149, Trieste, Italy. |
| المصدر: | Tumour virus research [Tumour Virus Res] 2023 Jun; Vol. 15, pp. 200257. Date of Electronic Publication: 2023 Feb 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101775149 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-6790 (Electronic) Linking ISSN: 26666790 NLM ISO Abbreviation: Tumour Virus Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2021]- |
| مواضيع طبية MeSH: | Papillomavirus Infections* , Oncogene Proteins, Viral*/genetics, Humans ; Phosphorylation ; 14-3-3 Proteins/genetics |
| مستخلص: | Previous studies have shown that the high-risk HPV E6 oncoprotein PDZ binding motifs (PBMs) can interact with PDZ proteins or members of the 14-3-3 family, depending upon the E6 phosphorylation status. However, different HPV E6 oncoproteins are subjected to phosphorylation by different cellular kinases. We have therefore been interested in determining whether we can dissect E6's PDZ and 14-3-3 interactions at the molecular level. Using HPV-18 E6, we have found that its Chk1 phosphorylation requires residues both upstream and downstream of the phospho-acceptor site, in addition to the Chk1 consensus recognition motif. Furthermore, we demonstrate that different high-risk HPV E6 types are differentially phosphorylated by Chk1 kinases, potentially due to the differences in their carboxy-terminal residues, as they are critical for kinase recognition. Moreover, differences in the E6 phosphorylation levels of different HR HPV types directly link to their ability to interact with different 14-3-3 isoforms, based on their phospho-status. Interestingly, 14-3-3 recognition appears to be less dependent upon the precise sequence constraints of the E6 carboxy terminal region, whilst minor amino acid variations have a major impact upon PDZ recognition. These results demonstrate that changes in E6 phospho-status during the life cycle or during malignant progression will modulate E6 interactions and, potentially, inversely regulate the levels of PDZ and 14-3-3 proteins. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: 14-3-3; E6; HPV; PDZ; Phosphorylation |
| المشرفين على المادة: | 0 (Oncogene Proteins, Viral) 0 (14-3-3 Proteins) |
| تواريخ الأحداث: | Date Created: 20230212 Date Completed: 20230605 Latest Revision: 20230611 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC10009279 |
| DOI: | 10.1016/j.tvr.2023.200257 |
| PMID: | 36775199 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2666-6790 |
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| DOI: | 10.1016/j.tvr.2023.200257 |