dc.creator | Nielsen, Casey Paulasue | |
dc.date.accessioned | 2020-08-22T20:49:30Z | |
dc.date.available | 2019-09-09 | |
dc.date.issued | 2019-09-09 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-08192019-173731 | |
dc.identifier.uri | http://hdl.handle.net/1803/13952 | |
dc.description.abstract | The 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.format.mimetype | application/pdf | |
dc.subject | Ubiquitin proteasome system | |
dc.subject | Cell signaling | |
dc.subject | WNT pathway | |
dc.subject | ubiquitin rheostat | |
dc.subject | breast cancer cells | |
dc.subject | deubiquitylases | |
dc.title | Regulation of WNT pathway specification by
DUB-E3 interactions | |
dc.type | dissertation | |
dc.contributor.committeeMember | Jason MacGurn | |
dc.contributor.committeeMember | Barbara Fingleton | |
dc.contributor.committeeMember | Ian Macara | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2019-09-09 | |
local.embargo.lift | 2019-09-09 | |
dc.contributor.committeeChair | Andrea Page-McCaw | |