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Regulation of WNT pathway specification by DUB-E3 interactions

dc.creatorNielsen, Casey Paulasue
dc.description.abstractThe WNT signaling network is comprised of multiple receptors that relay various input signals via distinct transduction pathways to execute multiple complex and context-specific output processes. Integrity of the WNT signaling network relies on proper specification between canonical and non-canonical pathways, which presents a regulatory challenge given that several signal transducing elements are shared between pathways. Here, we report that USP9X, a deubiquitylase, and WWP1, an E3 ubiquitin ligase, regulate a ubiquitin rheostat on DVL2, a WNT signaling protein. Our findings indicate that USP9X-mediated deubiquitylation of DVL2 is required for canonical WNT activation, while increased DVL2 ubiquitylation is associated with localization to actin-rich projections and activation of the planar cell polarity (PCP) pathway. We propose that a WWP1-USP9X axis regulates a ubiquitin rheostat on DVL2 that specifies its participation in either canonical WNT or WNT-PCP pathways. These findings have important implications for therapeutic targeting of USP9X in human cancer.
dc.subjectUbiquitin proteasome system
dc.subjectCell signaling
dc.subjectWNT pathway
dc.subjectubiquitin rheostat
dc.subjectbreast cancer cells
dc.titleRegulation of WNT pathway specification by DUB-E3 interactions
dc.contributor.committeeMemberJason MacGurn
dc.contributor.committeeMemberBarbara Fingleton
dc.contributor.committeeMemberIan Macara
dc.type.materialtext and Developmental Biology University
dc.contributor.committeeChairAndrea Page-McCaw

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