Subunit Selective Degradation of WIZ, a Lenalidomide- and Pomalidomide-Dependent Substrate of E3 Ubiquitin Ligase CRL4CRBN

Citation

Yu, Helen (2019) Subunit Selective Degradation of WIZ, a Lenalidomide- and Pomalidomide-Dependent Substrate of E3 Ubiquitin Ligase CRL4CRBN. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z7PK-NH81. https://resolver.caltech.edu/CaltechTHESIS:04232019-210733826

Abstract

This dissertation is focused on identifying novel targets of immunomodulatory(IMiD) drugs. IMiDs are a class of drugs that are used to treat multiple myeloma.The first chapter is an introduction to the clinical use of IMiDs, as well as the proteincereblon (CRBN), the primary target of IMiDs. The second chapter describes worktowards the identification of a novel IMiD target, WIZ, that is regulated by CRBNin an IMiD dependent manner. Mass spectrometry was performed to identify novelbinding partners, and IMiD dependent regulation by CRBN was validated usingchemical and genetic methods. Understanding how these drugs work will informthe production of more potent and more selective drugs.

Thesis Files