{"id":{"repo_id":"tdl","oai_identifier":"oai:tdl-ir.tdl.org:2152.5/4447"},"canonical_url":"https://search.dev.ndltd.org/etd/tdl/oai:tdl-ir.tdl.org:2152.5/4447","repository":{"repo_id":"tdl","name":"Texas Digital Library","base_url":"https://tdl-ir.tdl.org/server/oai/request"},"display":{"title":"The Cancer Specific Ubiquitin Ligase MAGE-A3/6-TRIM28 Drives Tumorigenesis by Ubiquitination and Proteasomal Degradation of AMPK","abstract":"The genes MAGE-A3 and MAGE-A6 (MAGE-A3/6) have a unique expression pattern in which they are normally expressed in the adult testis but are aberrantly expressed in cancer. It is known that when expressed in cancer, MAGE-A3/6 is a negative prognostic indicator and cancer cells are dependent on it for survival. Using the knowledge that MAGE-A3/6 binds and regulates the E3 ubiquitin ligase TRIM28, I investigated its biochemical role in cancer. I used unbiased methods to identify 19 novel substrates of MAGE-A3/6-TRIM28, including the known tumor suppressor AMPK. Ubiquitination of AMPK by MAGE-A3/6-TRIM28 induces its proteasomal degradation, thereby enhancing mTOR signaling and inhibiting autophagy within cells. Through this modulation of AMPK, MAGE-A3/6 is also able to act as an oncogene, inducing anchorage independent growth and the growth of tumors in vivo. Understanding the mechanism by which MAGE-A3/6 acts as an oncogene has revealed potential avenues of therapeutic intervention. Treatment of MAGE-A3/6 expressing cells with AMPK agonists reverses oncogenic properties in vitro. Ultimately, these studies have revealed how a germline protein functions in cancer and the potential points for therapeutic intervention.","abstract_html":"The genes MAGE-A3 and MAGE-A6 (MAGE-A3/6) have a unique expression pattern in which they are normally expressed in the adult testis but are aberrantly expressed in cancer. It is known that when expressed in cancer, MAGE-A3/6 is a negative prognostic indicator and cancer cells are dependent on it for survival. Using the knowledge that MAGE-A3/6 binds and regulates the E3 ubiquitin ligase TRIM28, I investigated its biochemical role in cancer. I used unbiased methods to identify 19 novel substrates of MAGE-A3/6-TRIM28, including the known tumor suppressor AMPK. Ubiquitination of AMPK by MAGE-A3/6-TRIM28 induces its proteasomal degradation, thereby enhancing mTOR signaling and inhibiting autophagy within cells. Through this modulation of AMPK, MAGE-A3/6 is also able to act as an oncogene, inducing anchorage independent growth and the growth of tumors in vivo. Understanding the mechanism by which MAGE-A3/6 acts as an oncogene has revealed potential avenues of therapeutic intervention. Treatment of MAGE-A3/6 expressing cells with AMPK agonists reverses oncogenic properties in vitro. Ultimately, these studies have revealed how a germline protein functions in cancer and the potential points for therapeutic intervention.","abstract_has_math":false,"creators":["Pineda, Carlos Tyler"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Yu, Hongtao","Levine, Beth","White, Michael A.","Potts, Patrick Ryan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-08-27","date_published":"2015-08-27","updated_at":"2026-07-27T21:19:11Z","subjects":["AMP-Activated Protein Kinases","Antigens, Neoplasm","Neoplasm Proteins","Neoplasms","Ubiquitination","Ubiquitin-Protein Ligases"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1017760194"],"render_values":[{"text":"1017760194","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/4447","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Yu, Hongtao","Levine, Beth","White, Michael A.","Potts, Patrick Ryan"]},{"key":"dc:creator","label":"Author","values":["Pineda, Carlos Tyler"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-01-04T21:09:36Z","2026-03-25T17:21:51Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-01-04T21:09:36Z"]},{"key":"dc:date.issued","label":"Date","values":["2015-08-27"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["AMP-Activated Protein Kinases","Antigens, Neoplasm","Neoplasm Proteins","Neoplasms","Ubiquitination","Ubiquitin-Protein Ligases"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/4447","1017760194"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.5/4447"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The genes MAGE-A3 and MAGE-A6 (MAGE-A3/6) have a unique expression pattern in which they are normally expressed in the adult testis but are aberrantly expressed in cancer. It is known that when expressed in cancer, MAGE-A3/6 is a negative prognostic indicator and cancer cells are dependent on it for survival. Using the knowledge that MAGE-A3/6 binds and regulates the E3 ubiquitin ligase TRIM28, I investigated its biochemical role in cancer. I used unbiased methods to identify 19 novel substrates of MAGE-A3/6-TRIM28, including the known tumor suppressor AMPK. Ubiquitination of AMPK by MAGE-A3/6-TRIM28 induces its proteasomal degradation, thereby enhancing mTOR signaling and inhibiting autophagy within cells. Through this modulation of AMPK, MAGE-A3/6 is also able to act as an oncogene, inducing anchorage independent growth and the growth of tumors in vivo. Understanding the mechanism by which MAGE-A3/6 acts as an oncogene has revealed potential avenues of therapeutic intervention. Treatment of MAGE-A3/6 expressing cells with AMPK agonists reverses oncogenic properties in vitro. Ultimately, these studies have revealed how a germline protein functions in cancer and the potential points for therapeutic intervention."]},{"key":"dc:title","label":"Title","values":["The Cancer Specific Ubiquitin Ligase MAGE-A3/6-TRIM28 Drives Tumorigenesis by Ubiquitination and Proteasomal Degradation of AMPK"]}]}],"canonical_facts":{"dc:contributor":["Yu, Hongtao","Levine, Beth","White, Michael A.","Potts, Patrick Ryan"],"dc:creator":["Pineda, Carlos Tyler"],"dc:date.accessioned":["2018-01-04T21:09:36Z","2026-03-25T17:21:51Z"],"dc:date.available":["2018-01-04T21:09:36Z"],"dc:date.issued":["2015-08-27"],"dc:description.abstract":["The genes MAGE-A3 and MAGE-A6 (MAGE-A3/6) have a unique expression pattern in which they are normally expressed in the adult testis but are aberrantly expressed in cancer. It is known that when expressed in cancer, MAGE-A3/6 is a negative prognostic indicator and cancer cells are dependent on it for survival. Using the knowledge that MAGE-A3/6 binds and regulates the E3 ubiquitin ligase TRIM28, I investigated its biochemical role in cancer. I used unbiased methods to identify 19 novel substrates of MAGE-A3/6-TRIM28, including the known tumor suppressor AMPK. Ubiquitination of AMPK by MAGE-A3/6-TRIM28 induces its proteasomal degradation, thereby enhancing mTOR signaling and inhibiting autophagy within cells. Through this modulation of AMPK, MAGE-A3/6 is also able to act as an oncogene, inducing anchorage independent growth and the growth of tumors in vivo. Understanding the mechanism by which MAGE-A3/6 acts as an oncogene has revealed potential avenues of therapeutic intervention. Treatment of MAGE-A3/6 expressing cells with AMPK agonists reverses oncogenic properties in vitro. Ultimately, these studies have revealed how a germline protein functions in cancer and the potential points for therapeutic intervention."],"dc:identifier":["https://hdl.handle.net/2152.5/4447","1017760194"],"dc:identifier.uri":["https://hdl.handle.net/2152.5/4447"],"dc:language":["en"],"dc:subject":["AMP-Activated Protein Kinases","Antigens, Neoplasm","Neoplasm Proteins","Neoplasms","Ubiquitination","Ubiquitin-Protein Ligases"],"dc:title":["The Cancer Specific Ubiquitin Ligase MAGE-A3/6-TRIM28 Drives Tumorigenesis by Ubiquitination and Proteasomal Degradation of AMPK"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:19:11Z"}