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Study Findings from F. Hans et al Provide New Insights into Ubiquitins (UBE2E Ubiquitin-conjugating Enzymes and Ubiquitin Isopeptidase Y Regulate...

August 20, 2014



Study Findings from F. Hans et al Provide New Insights into Ubiquitins (UBE2E Ubiquitin-conjugating Enzymes and Ubiquitin Isopeptidase Y Regulate TDP-43 Protein Ubiquitination)

By a News Reporter-Staff News Editor at Biotech Week -- Researchers detail new data in Proteins. According to news originating from Aachen, Germany, by NewsRx correspondents, research stated, "Trans-activation element DNA-binding protein of 43 kDa (TDP-43) characterizes insoluble protein aggregates in distinct subtypes of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 mediates many RNA processing steps within distinct protein complexes."

Our news journalists obtained a quote from the research, "Here we identify novel TDP-43 protein interactors found in a yeast two-hybrid screen using an adult human brain cDNA library. We confirmed the TDP-43 interaction of seven hits by co-immunoprecipitation and assessed their co-localization in HEK293E cells. As pathological TDP-43 is ubiquitinated, we focused on the ubiquitin- conjugating enzyme UBE2E3 and the ubiquitin isopeptidase Y (UBPY). When cells were treated with proteasome inhibitor, ubiquitinated and insoluble TDP-43 species accumulated. All three UBE2E family members could enhance the ubiquitination of TDP-43, whereas catalytically inactive UBE2E3(C145S) was much less efficient. Conversely, silencing of UBE2E3 reduced TDP-43 ubiquitination. We examined 15 of the 48 known disease-associated TDP-43 mutants and found that one was excessively ubiquitinated. This strong TDP-43(K263E) ubiquitination was further enhanced by proteasomal inhibition as well as UBE2E3 expression. Conversely, UBE2E3 silencing and expression of UBPY reduced TDP-43(K263E) ubiquitination. Moreover, wild-type but not active site mutant UBPY reduced ubiquitination of TDP-43 C-terminal fragments and of a nuclear import-impaired mutant. In Drosophila melanogaster, UBPY silencing enhanced neurodegenerative TDP-43 phenotypes and the accumulation of insoluble high molecular weight TDP-43 and ubiquitin species."

According to the news editors, the research concluded: "Thus, UBE2E3 and UBPY participate in the regulation of TDP-43 ubiquitination, solubility, and neurodegeneration."

For more information on this research see: UBE2E Ubiquitin-conjugating Enzymes and Ubiquitin Isopeptidase Y Regulate TDP-43 Protein Ubiquitination. Journal of Biological Chemistry, 2014;289(27):19164-19179. Journal of Biological Chemistry can be contacted at: Amer Soc Biochemistry Molecular Biology Inc, 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. (American Society for Biochemistry and Molecular Biology - www.asbmb.org; Journal of Biological Chemistry - www.jbc.org/)

The news correspondents report that additional information may be obtained from F. Hans, JARA, Translat Brain Med, D-52074 Aachen, Germany. Additional authors for this research include F.C. Fiesel, J.C. Strong, S. Jackel, T.M. Rasse, S. Geisler, W. Springer, J.B. Schulz, A. Voigt and P.J. Kahle (see also Proteins).

Keywords for this news article include: Aachen, Europe, Germany, Proteins, Ubiquitins

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Biotech Week


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