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BioE3 identifies specific substrates of ubiquitin E3 ligases

Author

Listed:
  • Orhi Barroso-Gomila

    (Bizkaia Technology Park)

  • Laura Merino-Cacho

    (Bizkaia Technology Park)

  • Veronica Muratore

    (Bizkaia Technology Park)

  • Coralia Perez

    (Bizkaia Technology Park)

  • Vincenzo Taibi

    (The AIRC Institute of Molecular Oncology)

  • Elena Maspero

    (The AIRC Institute of Molecular Oncology)

  • Mikel Azkargorta

    (Bizkaia Technology Park
    Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5)

  • Ibon Iloro

    (Bizkaia Technology Park
    Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5)

  • Fredrik Trulsson

    (Leiden University Medical Center (LUMC))

  • Alfred C. O. Vertegaal

    (Leiden University Medical Center (LUMC))

  • Ugo Mayor

    (Basque Foundation for Science
    University of the Basque Country (UPV/EHU))

  • Felix Elortza

    (Bizkaia Technology Park
    Instituto de Salud Carlos III, C/ Monforte de Lemos 3-5)

  • Simona Polo

    (The AIRC Institute of Molecular Oncology
    Università degli Studi di Milano)

  • Rosa Barrio

    (Bizkaia Technology Park)

  • James D. Sutherland

    (Bizkaia Technology Park)

Abstract

Hundreds of E3 ligases play a critical role in recognizing specific substrates for modification by ubiquitin (Ub). Separating genuine targets of E3s from E3-interactors remains a challenge. We present BioE3, a powerful approach for matching substrates to Ub E3 ligases of interest. Using BirA-E3 ligase fusions and bioUb, site-specific biotinylation of Ub-modified substrates of particular E3s facilitates proteomic identification. We show that BioE3 identifies both known and new targets of two RING-type E3 ligases: RNF4 (DNA damage response, PML bodies), and MIB1 (endocytosis, autophagy, centrosome dynamics). Versatile BioE3 identifies targets of an organelle-specific E3 (MARCH5) and a relatively uncharacterized E3 (RNF214). Furthermore, BioE3 works with NEDD4, a HECT-type E3, identifying new targets linked to vesicular trafficking. BioE3 detects altered specificity in response to chemicals, opening avenues for targeted protein degradation, and may be applicable for other Ub-likes (UbLs, e.g., SUMO) and E3 types. BioE3 applications shed light on cellular regulation by the complex UbL network.

Suggested Citation

  • Orhi Barroso-Gomila & Laura Merino-Cacho & Veronica Muratore & Coralia Perez & Vincenzo Taibi & Elena Maspero & Mikel Azkargorta & Ibon Iloro & Fredrik Trulsson & Alfred C. O. Vertegaal & Ugo Mayor & , 2023. "BioE3 identifies specific substrates of ubiquitin E3 ligases," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43326-8
    DOI: 10.1038/s41467-023-43326-8
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    References listed on IDEAS

    as
    1. Ramesh Kumar & Román González-Prieto & Zhenyu Xiao & Matty Verlaan-de Vries & Alfred C. O. Vertegaal, 2017. "The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    2. Hao Gu & Qidong Li & Shan Huang & Weiguang Lu & Fangyuan Cheng & Ping Gao & Chen Wang & Lin Miao & Yide Mei & Mian Wu, 2015. "Mitochondrial E3 ligase March5 maintains stemness of mouse ES cells via suppression of ERK signalling," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    Full references (including those not matched with items on IDEAS)

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