Show simple item record

dc.contributor.authorIyengar, P.
dc.contributor.authorJaynes, P.
dc.contributor.authorRodon, L.
dc.contributor.authorLama, D.
dc.contributor.authorLaw, K.
dc.contributor.authorLim, Y.
dc.contributor.authorVerma, C.
dc.contributor.authorSeoane, J.
dc.contributor.authorEichhorn, Pieter
dc.date.accessioned2018-12-13T09:15:08Z
dc.date.available2018-12-13T09:15:08Z
dc.date.created2018-12-12T02:47:09Z
dc.date.issued2015
dc.identifier.citationIyengar, P. and Jaynes, P. and Rodon, L. and Lama, D. and Law, K. and Lim, Y. and Verma, C. et al. 2015. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Scientific Reports. 5: 14733.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/73022
dc.identifier.doi10.1038/srep14733
dc.description.abstract

Ubiquitin modification of the TGF-ß pathway components is emerging as a key mechanism of TGF-ß pathway regulation. To limit TGF-ß responses, TGF-ß signaling is regulated through a negative feedback loop whereby the E3 ligase SMURF2 targets the TGF-ß receptor (TßR) complex for ubiquitin-mediated degradation. Counteracting this process, a number of deubiquitinating (DUBs) enzymes have recently been identified that deubiquitinate and stabilize the TßR. However the precise mechanism by which these DUBs act on TßR function remains poorly defined. Here, we demonstrate that apart from targeting the TßR complex directly, USP15 also deubiquitinates SMURF2 resulting in enhanced TßR stability and downstream pathway activation. Through proteomic analysis, we show that USP15 modulates the ubiquitination of Lys734, a residue required for SMURF2 catalytic activity. Our results show that SMURF2 is a critical target of USP15 in the TGF-ß pathway and may also explain how USP15 and SMURF2 target multiple complementary protein complexes in other pathways.

dc.publisherNature Publishing Group
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleUSP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination
dc.typeJournal Article
dcterms.source.volume5
dcterms.source.issn2045-2322
dcterms.source.titleScientific Reports
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access via publisher


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/