High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines

The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the development of cervical cancer. Besides its determinant role in carcinogenic progression, HPV E6 oncoprotein has also been instrumental in elucidating fundamental aspects of p53 function and its ubiquitin-proteasome degradation...

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Autores principales:	García Alai, María, Smal, Clara, de Prat Gay, Gonzalo
Publicado:	2007
Materias:	Antibodies Biodegradation Cells Monomers Oligomers Oncology Carcinogenic progression Cervical cancer Endogenous protein Ubiquitin-proteasome degradation Proteins oligomer PDZ protein proteasome protein antibody protein E6 protein p53 recombinant protein ubiquitin article cancer growth carcinogenesis cell line cell nucleus cellular distribution controlled study DNA tumor virus embryo HeLa cell human human cell nonhuman particle size priority journal protein analysis protein assembly protein binding protein conformation protein degradation protein denaturation protein domain protein function protein localization protein quaternary structure protein targeting protein tertiary structure protein transport serum structural proteomics thermostability uterine cervix cancer virus cell transformation virus strain virus typing Wart virus Base Sequence Cell Line, Transformed Cell Transformation, Neoplastic Cell Transformation, Viral DNA, Viral DNA-Binding Proteins Female Human papillomavirus 16 Human papillomavirus 18 Humans Models, Biological Multiprotein Complexes Oncogene Proteins, Viral Protein Folding Protein Structure, Quaternary Repressor Proteins Tumor Suppressor Protein p53 Uterine Cervical Neoplasms Human papillomavirus
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v46_n2_p341_GarciaAlai http://hdl.handle.net/20.500.12110/paper_00062960_v46_n2_p341_GarciaAlai
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00062960_v46_n2_p341_GarciaAlai
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spelling	paper:paper_00062960_v46_n2_p341_GarciaAlai2023-06-08T14:30:40Z High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines García Alai, María Smal, Clara de Prat Gay, Gonzalo Antibodies Biodegradation Cells Monomers Oligomers Oncology Carcinogenic progression Cervical cancer Endogenous protein Ubiquitin-proteasome degradation Proteins oligomer PDZ protein proteasome protein antibody protein E6 protein p53 recombinant protein ubiquitin article cancer growth carcinogenesis cell line cell nucleus cellular distribution controlled study DNA tumor virus embryo HeLa cell human human cell nonhuman particle size priority journal protein analysis protein assembly protein binding protein conformation protein degradation protein denaturation protein domain protein function protein localization protein quaternary structure protein targeting protein tertiary structure protein transport serum structural proteomics thermostability uterine cervix cancer virus cell transformation virus strain virus typing Wart virus Base Sequence Cell Line, Transformed Cell Transformation, Neoplastic Cell Transformation, Viral DNA, Viral DNA-Binding Proteins Female Human papillomavirus 16 Human papillomavirus 18 Humans Models, Biological Multiprotein Complexes Oncogene Proteins, Viral Protein Folding Protein Structure, Quaternary Repressor Proteins Tumor Suppressor Protein p53 Uterine Cervical Neoplasms Human papillomavirus The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the development of cervical cancer. Besides its determinant role in carcinogenic progression, HPV E6 oncoprotein has also been instrumental in elucidating fundamental aspects of p53 function and its ubiquitin-proteasome degradation, with counterpart activities in various DNA tumor viruses. Establishing the conformational state and cellular distribution unequivocally for the endogenous protein in HPV-transformed cell lines derived from carcinomas is essential for understanding the underlying mechanism. Recombinant E6 from high-risk strains 16 and 18 folds into soluble oligomers of ∼1.2 MDa, which are thermostable and display cooperative loss of tertiary and secondary structure upon chemical denaturation. Antibodies raised against these assemblies locate E6 evenly distributed in the cells. By depleting the polyclonal serum by immunoblocking with monomeric E6, the nuclei of Hela and CaSki cells become completely devoid of label, indicating that monomeric species are mainly localized in the nucleus and that both monomers and oligomers share epitopes. The monomeric species promote degradation of p53 by the proteasome, which correlates with the nuclear localization we describe. In contrast, the oligomeric E6 does not promote p53 degradation, in agreement with its cytoplasmic localization inferred from the immunoneutralization experiments. Our results indicate that the cytoplasmic species contain conformational epitopes that may arise from yet undefined homo or hetero-oligomers, but its localization otherwise agrees with that of the other group of major E6 targets, those involving PDZ binding domains, which requires further investigation. © 2007 American Chemical Society. Fil:García-Alai, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Smal, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:De Prat-Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v46_n2_p341_GarciaAlai http://hdl.handle.net/20.500.12110/paper_00062960_v46_n2_p341_GarciaAlai
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Antibodies Biodegradation Cells Monomers Oligomers Oncology Carcinogenic progression Cervical cancer Endogenous protein Ubiquitin-proteasome degradation Proteins oligomer PDZ protein proteasome protein antibody protein E6 protein p53 recombinant protein ubiquitin article cancer growth carcinogenesis cell line cell nucleus cellular distribution controlled study DNA tumor virus embryo HeLa cell human human cell nonhuman particle size priority journal protein analysis protein assembly protein binding protein conformation protein degradation protein denaturation protein domain protein function protein localization protein quaternary structure protein targeting protein tertiary structure protein transport serum structural proteomics thermostability uterine cervix cancer virus cell transformation virus strain virus typing Wart virus Base Sequence Cell Line, Transformed Cell Transformation, Neoplastic Cell Transformation, Viral DNA, Viral DNA-Binding Proteins Female Human papillomavirus 16 Human papillomavirus 18 Humans Models, Biological Multiprotein Complexes Oncogene Proteins, Viral Protein Folding Protein Structure, Quaternary Repressor Proteins Tumor Suppressor Protein p53 Uterine Cervical Neoplasms Human papillomavirus
spellingShingle	Antibodies Biodegradation Cells Monomers Oligomers Oncology Carcinogenic progression Cervical cancer Endogenous protein Ubiquitin-proteasome degradation Proteins oligomer PDZ protein proteasome protein antibody protein E6 protein p53 recombinant protein ubiquitin article cancer growth carcinogenesis cell line cell nucleus cellular distribution controlled study DNA tumor virus embryo HeLa cell human human cell nonhuman particle size priority journal protein analysis protein assembly protein binding protein conformation protein degradation protein denaturation protein domain protein function protein localization protein quaternary structure protein targeting protein tertiary structure protein transport serum structural proteomics thermostability uterine cervix cancer virus cell transformation virus strain virus typing Wart virus Base Sequence Cell Line, Transformed Cell Transformation, Neoplastic Cell Transformation, Viral DNA, Viral DNA-Binding Proteins Female Human papillomavirus 16 Human papillomavirus 18 Humans Models, Biological Multiprotein Complexes Oncogene Proteins, Viral Protein Folding Protein Structure, Quaternary Repressor Proteins Tumor Suppressor Protein p53 Uterine Cervical Neoplasms Human papillomavirus García Alai, María Smal, Clara de Prat Gay, Gonzalo High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
topic_facet	Antibodies Biodegradation Cells Monomers Oligomers Oncology Carcinogenic progression Cervical cancer Endogenous protein Ubiquitin-proteasome degradation Proteins oligomer PDZ protein proteasome protein antibody protein E6 protein p53 recombinant protein ubiquitin article cancer growth carcinogenesis cell line cell nucleus cellular distribution controlled study DNA tumor virus embryo HeLa cell human human cell nonhuman particle size priority journal protein analysis protein assembly protein binding protein conformation protein degradation protein denaturation protein domain protein function protein localization protein quaternary structure protein targeting protein tertiary structure protein transport serum structural proteomics thermostability uterine cervix cancer virus cell transformation virus strain virus typing Wart virus Base Sequence Cell Line, Transformed Cell Transformation, Neoplastic Cell Transformation, Viral DNA, Viral DNA-Binding Proteins Female Human papillomavirus 16 Human papillomavirus 18 Humans Models, Biological Multiprotein Complexes Oncogene Proteins, Viral Protein Folding Protein Structure, Quaternary Repressor Proteins Tumor Suppressor Protein p53 Uterine Cervical Neoplasms Human papillomavirus
description	The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the development of cervical cancer. Besides its determinant role in carcinogenic progression, HPV E6 oncoprotein has also been instrumental in elucidating fundamental aspects of p53 function and its ubiquitin-proteasome degradation, with counterpart activities in various DNA tumor viruses. Establishing the conformational state and cellular distribution unequivocally for the endogenous protein in HPV-transformed cell lines derived from carcinomas is essential for understanding the underlying mechanism. Recombinant E6 from high-risk strains 16 and 18 folds into soluble oligomers of ∼1.2 MDa, which are thermostable and display cooperative loss of tertiary and secondary structure upon chemical denaturation. Antibodies raised against these assemblies locate E6 evenly distributed in the cells. By depleting the polyclonal serum by immunoblocking with monomeric E6, the nuclei of Hela and CaSki cells become completely devoid of label, indicating that monomeric species are mainly localized in the nucleus and that both monomers and oligomers share epitopes. The monomeric species promote degradation of p53 by the proteasome, which correlates with the nuclear localization we describe. In contrast, the oligomeric E6 does not promote p53 degradation, in agreement with its cytoplasmic localization inferred from the immunoneutralization experiments. Our results indicate that the cytoplasmic species contain conformational epitopes that may arise from yet undefined homo or hetero-oligomers, but its localization otherwise agrees with that of the other group of major E6 targets, those involving PDZ binding domains, which requires further investigation. © 2007 American Chemical Society.
author	García Alai, María Smal, Clara de Prat Gay, Gonzalo
author_facet	García Alai, María Smal, Clara de Prat Gay, Gonzalo
author_sort	García Alai, María
title	High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
title_short	High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
title_full	High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
title_fullStr	High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
title_full_unstemmed	High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines
title_sort	high-risk hpv e6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic hpv-transformed cell lines
publishDate	2007
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v46_n2_p341_GarciaAlai http://hdl.handle.net/20.500.12110/paper_00062960_v46_n2_p341_GarciaAlai
work_keys_str_mv	AT garciaalaimaria highriskhpve6oncoproteinsassembleintolargeoligomersthatallowlocalizationofendogenousspeciesinprototypichpvtransformedcelllines AT smalclara highriskhpve6oncoproteinsassembleintolargeoligomersthatallowlocalizationofendogenousspeciesinprototypichpvtransformedcelllines AT depratgaygonzalo highriskhpve6oncoproteinsassembleintolargeoligomersthatallowlocalizationofendogenousspeciesinprototypichpvtransformedcelllines
_version_	1768543541754068992

High-risk HPV E6 oncoproteins assemble into large oligomers that allow localization of endogenous species in prototypic HPV-transformed cell lines

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