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ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail

Author

Listed:
  • M. Teresa Bertran

    (The Francis Crick Institute)

  • Stéphane Mouilleron

    (The Francis Crick Institute)

  • Yanxiang Zhou

    (The Francis Crick Institute)

  • Rakhi Bajaj

    (University of Arizona)

  • Federico Uliana

    (Institute of Molecular Systems Biology, ETH Zürich)

  • Ganesan Senthil Kumar

    (University of Arizona)

  • Audrey Drogen

    (Institute of Molecular Systems Biology, ETH Zürich)

  • Rebecca Lee

    (The Francis Crick Institute)

  • Jennifer J. Banerjee

    (The Francis Crick Institute)

  • Simon Hauri

    (Institute of Molecular Systems Biology, ETH Zürich)

  • Nicola O’Reilly

    (Peptide Chemistry Laboratory, The Francis Crick Institute)

  • Matthias Gstaiger

    (Institute of Molecular Systems Biology, ETH Zürich)

  • Rebecca Page

    (University of Arizona)

  • Wolfgang Peti

    (University of Arizona)

  • Nicolas Tapon

    (The Francis Crick Institute)

Abstract

Serine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.

Suggested Citation

  • M. Teresa Bertran & Stéphane Mouilleron & Yanxiang Zhou & Rakhi Bajaj & Federico Uliana & Ganesan Senthil Kumar & Audrey Drogen & Rebecca Lee & Jennifer J. Banerjee & Simon Hauri & Nicola O’Reilly & M, 2019. "ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08686-0
    DOI: 10.1038/s41467-019-08686-0
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    Cited by:

    1. Gautam Srivastava & Meng S. Choy & Nicolas Bolik-Coulon & Rebecca Page & Wolfgang Peti, 2023. "Inhibitor-3 inhibits Protein Phosphatase 1 via a metal binding dynamic protein–protein interaction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Sarah Lemaire & Mónica Ferreira & Zander Claes & Rita Derua & Madryn Lake & Gerd Hoeven & Fabienne Withof & Xinyu Cao & Elora C. Greiner & Arminja N. Kettenbach & Aleyde Eynde & Mathieu Bollen, 2024. "PPP1R2 stimulates protein phosphatase-1 through stabilisation of dynamic subunit interactions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Christophe Royer & Elizabeth Sandham & Elizabeth Slee & Falk Schneider & Christoffer B. Lagerholm & Jonathan Godwin & Nisha Veits & Holly Hathrell & Felix Zhou & Karolis Leonavicius & Jemma Garratt & , 2022. "ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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