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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18292

Title: Regulation of the 3BP2 Adaptor Protein by the Nedd4 Family of HECT E3 Ubiquitin Ligases
Authors: Gabrielli, Lisa Marie
Advisor: Rottapel, Robert
Department: Medical Biophysics
Keywords: 3BP2
Issue Date: 18-Jan-2010
Abstract: 3BP2 has been previously described as the protein mutated in the osteoporotic disorder, Cherubism. The gain of function mutation that characterizes Cherubism is the result of an uncoupling of its interaction with Tankyrase 2, which has been reported to stimulate 3BP2 ubiquitination. Here we describe an attempt at identifying the E3 ligase responsible for mediating this ubiquitination using four candidate members from the Nedd4 family. Based on their respective abilities to bind and ubiquitinate 3BP2, as well as their sensitivity to the presence of Tankyrase 2 and to 3BP2 mutations (including Cherubism mutations and mutations within the 3BP2 PPxY motif thought to confer binding to the Nedd4 proteins), we have determined that Smurf1 best fits our model. Further supporting these findings, we have seen an elevation in 3BP2 protein levels in macrophages derived from Smurf1-/-/Smurf2+/- mice. This work supports a role for the Nedd4 family member, Smurf1, in mediating 3BP2 ubiquitination.
URI: http://hdl.handle.net/1807/18292
Appears in Collections:Master
Department of Medical Biophysics - Master theses

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