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1.  Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling 
Oncogenesis  2013;2(8):e64-.
Dishevelled (Dvl) is a key regulator of Wnt signaling both in the canonical and non-canonical pathways. Here we report the identification of a regulatory domain of ubiquitination (RDU) in the C-terminus of Dvl. Mutations in the RDU resulted in accumulation of polyubiquitinated forms of Dvl, which were mainly K63 linked. Small interfering RNA-based screening identified Usp14 as a mediator of Dvl deubiquitination. Genetic and chemical suppression of Usp14 activity caused an increase in Dvl polyubiquitination and significantly impaired downstream Wnt signaling. These data suggest that Usp14 functions as a positive regulator of the Wnt signaling pathway. Consistently, tissue microarray analysis of colon cancer revealed a strong correlation between the levels of Usp14 and β-catenin, which suggests an oncogenic role for Usp14 via enhancement of Wnt/β-catenin signaling.
doi:10.1038/oncsis.2013.28
PMCID: PMC3759127  PMID: 23958854
Wnt; dishevelled; deubiquitinase; Usp14; ubiquitination
2.  Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer? 
The Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized.
doi:10.1007/s10549-008-0059-5
PMCID: PMC2697904  PMID: 18500672
Breast cancer; glycoprotein; iodide uptake; radionuclide imaging and therapy; sodium iodide symporter (NIS)
3.  Specificity of DNA binding activity of the Bacillus subtilis catabolite control protein CcpA. 
Journal of Bacteriology  1995;177(17):5129-5134.
CcpA was purified from Escherichia coli BL21 (lambda DE3)/pLysS carrying plasmid pTSC5, which was constructed by inserting the ccpA gene into the polycloning site of pGEM4. The purified protein migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent mass of 38 kDa but was eluted from a calibrated Bio-Gel P-100 column with an apparent mass of 75 kDa. Western blot (immunoblot) analysis revealed the presence of CcpA in E. coli BL21 (lambda DE3)/pLysS/pTSC5, which carries ccpA, and in wild-type Bacillus subtilis 168 but not in E. coli BL21 (lambda DE3)/pLysS/pGEM4 or in B. subtilis WLN-29, in which ccpA is inactivated by transposon Tn917 insertion. Purified CcpA bound to DNA containing amyO and retarded its mobility in electrophoretic mobility shift analysis. Complete retardation of the DNA required 75 ng of CcpA per assay. In DNase protection analysis, CcpA bound to DNA containing amyO and protected a region spanning amyO when either DNA strand was labeled. Mutant forms of amyO not effective in catabolite repression were not retarded by CcpA.
PMCID: PMC177293  PMID: 7665492

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