Show simple item record

dc.contributor.advisorYu, Hongtaoen
dc.creatorPineda, Carlos Tyleren
dc.date.accessioned2018-01-04T21:09:36Z
dc.date.available2018-01-04T21:09:36Z
dc.date.created2015-12
dc.date.issued2015-08-27
dc.date.submittedDecember 2015
dc.identifier.urihttps://hdl.handle.net/2152.5/4447
dc.description.abstractThe 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.en
dc.format.mimetypeapplication/pdfen
dc.language.isoenen
dc.subjectAMP-Activated Protein Kinasesen
dc.subjectAntigens, Neoplasmen
dc.subjectNeoplasm Proteinsen
dc.subjectNeoplasmsen
dc.subjectUbiquitinationen
dc.subjectUbiquitin-Protein Ligasesen
dc.titleThe Cancer Specific Ubiquitin Ligase MAGE-A3/6-TRIM28 Drives Tumorigenesis by Ubiquitination and Proteasomal Degradation of AMPKen
dc.typeThesisen
dc.date.updated2018-01-04T21:03:35Z
dc.type.materialtexten
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
thesis.degree.disciplineCell Regulationen
dc.contributor.committeeMemberLevine, Bethen
dc.contributor.committeeMemberWhite, Michael A.en
dc.contributor.committeeMemberPotts, Paul Ryanen
dc.identifier.oclc1017760194


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record