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

Author

Listed:
  • Xianpeng Liu

    (Northwestern University)

  • Bo Zhao

    (University of Chicago
    School of Pharmacy, Shanghai Jiao Tong University)

  • Limin Sun

    (Northwestern University)

  • Karan Bhuripanyo

    (University of Chicago
    Center for Diagnostics & Therapeutics, Georgia State University)

  • Yiyang Wang

    (Center for Diagnostics & Therapeutics, Georgia State University)

  • Yingtao Bi

    (Northwestern University
    Present address: Abbvie Bioresearch Center, Worcester, Massachusetts 01605, USA)

  • Ramana V. Davuluri

    (Northwestern University
    Robert H. Lurie Comprehensive Cancer Center, Northwestern University)

  • Duc M. Duong

    (Integrated Proteomics Core, Emory University)

  • Dhaval Nanavati

    (Chemistry of Life Processes Institute, Northwestern University
    Present address: Abbvie Bioresearch Center, Worcester, Massachusetts 01605, USA)

  • Jun Yin

    (University of Chicago
    Center for Diagnostics & Therapeutics, Georgia State University)

  • Hiroaki Kiyokawa

    (Northwestern University
    Robert H. Lurie Comprehensive Cancer Center, Northwestern University)

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.

Suggested Citation

  • Xianpeng Liu & Bo Zhao & Limin Sun & Karan Bhuripanyo & Yiyang Wang & Yingtao Bi & Ramana V. Davuluri & Duc M. Duong & Dhaval Nanavati & Jun Yin & Hiroaki Kiyokawa, 2017. "Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14286
    DOI: 10.1038/ncomms14286
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    Cited by:

    1. Pierre C. Havugimana & Raghuveera Kumar Goel & Sadhna Phanse & Ahmed Youssef & Dzmitry Padhorny & Sergei Kotelnikov & Dima Kozakov & Andrew Emili, 2022. "Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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