Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18
| Autor: | Kyeong Sik Jin, Min Wook Kim, Bonsu Ku, Won Kon Kim, Eun-Woo Lee, Hye Seon Lee, Seung Jun Kim, Sang Chul Lee, Ho-Chul Shin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Proteasome Endopeptidase Complex Genotype viruses Papillomavirus E7 Proteins HPV18 Protein tyrosine phosphatase Alphapapillomavirus medicine.disease_cause law.invention HeLa law Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness Amino Acid Sequence human papillomavirus Molecular Biology E7 CR3 Cell Proliferation Gene knockdown biology Chemistry Cell Biology General Medicine PTPN21 biology.organism_classification Protein Tyrosine Phosphatases Non-Receptor Cell biology HaCaT Proteolysis Suppressor Carcinogenesis PTPN14 Research Article Protein Binding |
| Zdroj: | Molecules and Cells |
| ISSN: | 0219-1032 1016-8478 |
| Popis: | Human papillomaviruses (HPVs) cause cellular hyperproliferation-associated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a well-defined tumor suppressor, and found that this intermolecular interaction plays a key role in E7-driven transformation and tumorigenesis. In this study, we carried out a molecular analysis of the interaction between CR3 of HPV18 E7 and the PTP domain of PTPN21, a PTP protein that shares high sequence homology with PTPN14 but is putatively oncogenic rather than tumor-suppressive. Through the combined use of biochemical tools, we verified that HPV18 E7 and PTPN21 form a 2:2 complex, with a dissociation constant of 5 nM and a nearly identical binding manner with the HPV18 E7 and PTPN14 complex. Nevertheless, despite the structural similarities, the biological consequences of the E7 interaction were found to differ between the two PTP proteins. Unlike PTPN14, PTPN21 did not appear to be subjected to proteasomal degradation in HPV18-positive HeLa cervical cancer cells. Moreover, knockdown of PTPN21 led to retardation of the migration/invasion of HeLa cells and HPV18 E7-expressing HaCaT keratinocytes, which reflects its protumor activity. In conclusion, the associations of the viral oncoprotein E7 with PTPN14 and PTPN21 are similar at the molecular level but play different physiological roles. |
| Databáze: | OpenAIRE |
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