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Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes
- Source :
- Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017), Nature Communications
- Publication Year :
- 2017
- Publisher :
- Nature Portfolio, 2017.
-
Abstract
- Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Uba1 was thought to be the only E1 until the recent identification of Uba6. To differentiate the biological functions of Uba1 and Uba6, we applied an orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells. By expressing pairs of an engineered ubiquitin and engineered Uba1 or Uba6 that were generated for exclusive interactions, we identified 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps. Bioinformatics analysis reveals substantial differences in pathways involving Uba1- and Uba6-specific targets. We demonstrate that polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1, and that Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. These data suggest that distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6.<br />The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.
- Subjects :
- 0301 basic medicine
Proteasome Endopeptidase Complex
Ubiquitin-activating enzyme
Science
General Physics and Astronomy
Ubiquitin-Activating Enzymes
Ubiquitin-conjugating enzyme
General Biochemistry, Genetics and Molecular Biology
Article
Epithelium
Substrate Specificity
03 medical and health sciences
Ezrin
Ubiquitin
Cell Line, Tumor
Morphogenesis
Humans
RNA, Small Interfering
CELF1 Protein
Multidisciplinary
biology
HEK 293 cells
Ubiquitination
Computational Biology
Cell Differentiation
General Chemistry
UBA1
Protein ubiquitination
Ubiquitin ligase
Cytoskeletal Proteins
Mutagenesis, Insertional
030104 developmental biology
HEK293 Cells
Biochemistry
Proteolysis
biology.protein
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....e6311c44bfd0406886bedd0442fd55f5