Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes

Xianpeng Liu, Bo Zhao, Limin Sun, Karan Bhuripanyo, Yiyang Wang, Yingtao Bi, Ramana V. Davuluri, Duc M. Duong, Dhaval Nanavati, Jun Yin () and Hiroaki Kiyokawa ()
Additional contact information
Xianpeng Liu: Northwestern University
Bo Zhao: University of Chicago
Limin Sun: Northwestern University
Karan Bhuripanyo: University of Chicago
Yiyang Wang: Center for Diagnostics & Therapeutics, Georgia State University
Yingtao Bi: Northwestern University
Ramana V. Davuluri: Northwestern University
Duc M. Duong: Integrated Proteomics Core, Emory University
Dhaval Nanavati: Chemistry of Life Processes Institute, Northwestern University
Jun Yin: University of Chicago
Hiroaki Kiyokawa: Northwestern University

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms14286 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14286

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14286

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().