{"id":{"repo_id":"tdl","oai_identifier":"oai:tdl-ir.tdl.org:2152.3/11268"},"canonical_url":"https://search.dev.ndltd.org/etd/tdl/oai:tdl-ir.tdl.org:2152.3/11268","repository":{"repo_id":"tdl","name":"Texas Digital Library","base_url":"https://tdl-ir.tdl.org/server/oai/request"},"display":{"title":"THE ROLE OF E6 PROTEIN IN HUMAN PAPILLOMAVIRUS ASSOCIATED UPPER AIRWAY DISEASES","abstract":"Infection of the upper aero-digestive tract with low-risk and high-risk human papillomaviruses is the cause of recurrent respiratory papillomatosis and a subset of head and neck cancers, respectively. E6 protein is considered one of the oncoproteins encoded by high-risk HPVs, due to its ability to degrade tumor suppressor p53, activate telomerase, avoid apoptosis and other functions that contribute to carcinogenesis. Most of the functions of high-risk E6 proteins act through interaction with host cellular proteins, while little is known about the cellular interacting partners to low-risk E6 proteins. Here we used GST-pulldown coupled with mass spectrometry to identify potential cellular host proteins to E6 proteins from low-risk types 6 and 11 as well as high-risk type 16. We have identified 40 cellular proteins in complex with GST-6E6, 93 proteins with GST-11E6, and 179 proteins with GST-16E6. Among these bound proteins, we further confirmed SAMD9 as a novel interaction partner to low-risk HPV-11 E6 protein by using co-immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. SAMD9 is a host restriction factor for myxoma virus and vaccinia virus. We hypothesize that SAMD9 may have an anti-viral effect against HPV-11, which is still to be determined as we need to establish an efficient in vitro HPV-11 replication model. Due to the possibility that HPVs may maintain their genome in the infected host cells in a stem cell-like state to establish persistent infection, which can give rise to benign and malignant cancers, we have also investigated the effects of E6 proteins from a low-risk type HPV-6 and a high-risk type HPV-16 on stem cell-like properties in keratinocytes expressing these proteins. Increased tumor sphere number, ALDH enzyme activity, and elevated stem cell marker Oct4 expression were observed in HPV-16 E6- expressing cells, when compared to those of low-risk HPV-6 E6-expressing cells and control cells. Additionally, a significant increase of interleukin-6 (IL-6) expression was observed in HPV-16 E6-expressing cells. Neutralizing IL-6 can inhibit the Oct4 expression induced by HPV-16 E6 protein. Our study suggests that high-risk HPV-16 E6 upregulates IL-6 expression to promote stem cell-like properties.","abstract_html":"Infection of the upper aero-digestive tract with low-risk and high-risk human papillomaviruses is the cause of recurrent respiratory papillomatosis and a subset of head and neck cancers, respectively. E6 protein is considered one of the oncoproteins encoded by high-risk HPVs, due to its ability to degrade tumor suppressor p53, activate telomerase, avoid apoptosis and other functions that contribute to carcinogenesis. Most of the functions of high-risk E6 proteins act through interaction with host cellular proteins, while little is known about the cellular interacting partners to low-risk E6 proteins. Here we used GST-pulldown coupled with mass spectrometry to identify potential cellular host proteins to E6 proteins from low-risk types 6 and 11 as well as high-risk type 16. We have identified 40 cellular proteins in complex with GST-6E6, 93 proteins with GST-11E6, and 179 proteins with GST-16E6. Among these bound proteins, we further confirmed SAMD9 as a novel interaction partner to low-risk HPV-11 E6 protein by using co-immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. SAMD9 is a host restriction factor for myxoma virus and vaccinia virus. We hypothesize that SAMD9 may have an anti-viral effect against HPV-11, which is still to be determined as we need to establish an efficient in vitro HPV-11 replication model. Due to the possibility that HPVs may maintain their genome in the infected host cells in a stem cell-like state to establish persistent infection, which can give rise to benign and malignant cancers, we have also investigated the effects of E6 proteins from a low-risk type HPV-6 and a high-risk type HPV-16 on stem cell-like properties in keratinocytes expressing these proteins. Increased tumor sphere number, ALDH enzyme activity, and elevated stem cell marker Oct4 expression were observed in HPV-16 E6- expressing cells, when compared to those of low-risk HPV-6 E6-expressing cells and control cells. Additionally, a significant increase of interleukin-6 (IL-6) expression was observed in HPV-16 E6-expressing cells. Neutralizing IL-6 can inhibit the Oct4 expression induced by HPV-16 E6 protein. Our study suggests that high-risk HPV-16 E6 upregulates IL-6 expression to promote stem cell-like properties.","abstract_has_math":false,"creators":["Wang, Jia"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-27T21:19:01Z","subjects":["human papillomaviruses","E6 protein"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/11268","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Wang, Jia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-04-21T15:45:08Z","2026-06-09T21:36:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-04-21T15:45:08Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["human papillomaviruses","E6 protein"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.3/11268"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/11268"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Infection of the upper aero-digestive tract with low-risk and high-risk human papillomaviruses is the cause of recurrent respiratory papillomatosis and a subset of head and neck cancers, respectively. E6 protein is considered one of the oncoproteins encoded by high-risk HPVs, due to its ability to degrade tumor suppressor p53, activate telomerase, avoid apoptosis and other functions that contribute to carcinogenesis. Most of the functions of high-risk E6 proteins act through interaction with host cellular proteins, while little is known about the cellular interacting partners to low-risk E6 proteins. Here we used GST-pulldown coupled with mass spectrometry to identify potential cellular host proteins to E6 proteins from low-risk types 6 and 11 as well as high-risk type 16. We have identified 40 cellular proteins in complex with GST-6E6, 93 proteins with GST-11E6, and 179 proteins with GST-16E6. Among these bound proteins, we further confirmed SAMD9 as a novel interaction partner to low-risk HPV-11 E6 protein by using co-immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. SAMD9 is a host restriction factor for myxoma virus and vaccinia virus. We hypothesize that SAMD9 may have an anti-viral effect against HPV-11, which is still to be determined as we need to establish an efficient in vitro HPV-11 replication model. Due to the possibility that HPVs may maintain their genome in the infected host cells in a stem cell-like state to establish persistent infection, which can give rise to benign and malignant cancers, we have also investigated the effects of E6 proteins from a low-risk type HPV-6 and a high-risk type HPV-16 on stem cell-like properties in keratinocytes expressing these proteins. Increased tumor sphere number, ALDH enzyme activity, and elevated stem cell marker Oct4 expression were observed in HPV-16 E6- expressing cells, when compared to those of low-risk HPV-6 E6-expressing cells and control cells. Additionally, a significant increase of interleukin-6 (IL-6) expression was observed in HPV-16 E6-expressing cells. Neutralizing IL-6 can inhibit the Oct4 expression induced by HPV-16 E6 protein. Our study suggests that high-risk HPV-16 E6 upregulates IL-6 expression to promote stem cell-like properties."]},{"key":"dc:title","label":"Title","values":["THE ROLE OF E6 PROTEIN IN HUMAN PAPILLOMAVIRUS ASSOCIATED UPPER AIRWAY DISEASES"]}]}],"canonical_facts":{"dc:creator":["Wang, Jia"],"dc:date.accessioned":["2021-04-21T15:45:08Z","2026-06-09T21:36:01Z"],"dc:date.available":["2021-04-21T15:45:08Z"],"dc:description.abstract":["Infection of the upper aero-digestive tract with low-risk and high-risk human papillomaviruses is the cause of recurrent respiratory papillomatosis and a subset of head and neck cancers, respectively. E6 protein is considered one of the oncoproteins encoded by high-risk HPVs, due to its ability to degrade tumor suppressor p53, activate telomerase, avoid apoptosis and other functions that contribute to carcinogenesis. Most of the functions of high-risk E6 proteins act through interaction with host cellular proteins, while little is known about the cellular interacting partners to low-risk E6 proteins. Here we used GST-pulldown coupled with mass spectrometry to identify potential cellular host proteins to E6 proteins from low-risk types 6 and 11 as well as high-risk type 16. We have identified 40 cellular proteins in complex with GST-6E6, 93 proteins with GST-11E6, and 179 proteins with GST-16E6. Among these bound proteins, we further confirmed SAMD9 as a novel interaction partner to low-risk HPV-11 E6 protein by using co-immunoprecipitation, proximity ligation assay, and confocal immunofluorescence staining. SAMD9 is a host restriction factor for myxoma virus and vaccinia virus. We hypothesize that SAMD9 may have an anti-viral effect against HPV-11, which is still to be determined as we need to establish an efficient in vitro HPV-11 replication model. Due to the possibility that HPVs may maintain their genome in the infected host cells in a stem cell-like state to establish persistent infection, which can give rise to benign and malignant cancers, we have also investigated the effects of E6 proteins from a low-risk type HPV-6 and a high-risk type HPV-16 on stem cell-like properties in keratinocytes expressing these proteins. Increased tumor sphere number, ALDH enzyme activity, and elevated stem cell marker Oct4 expression were observed in HPV-16 E6- expressing cells, when compared to those of low-risk HPV-6 E6-expressing cells and control cells. Additionally, a significant increase of interleukin-6 (IL-6) expression was observed in HPV-16 E6-expressing cells. Neutralizing IL-6 can inhibit the Oct4 expression induced by HPV-16 E6 protein. Our study suggests that high-risk HPV-16 E6 upregulates IL-6 expression to promote stem cell-like properties."],"dc:identifier":["https://hdl.handle.net/2152.3/11268"],"dc:identifier.uri":["https://hdl.handle.net/2152.3/11268"],"dc:subject":["human papillomaviruses","E6 protein"],"dc:title":["THE ROLE OF E6 PROTEIN IN HUMAN PAPILLOMAVIRUS ASSOCIATED UPPER AIRWAY DISEASES"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:19:01Z"}