IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v414y2001i6863d10.1038_35107009.html
   My bibliography  Save this article

Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication

Author

Listed:
  • Piers Nash

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • Xiaojing Tang

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • Stephen Orlicky

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital)

  • Qinghua Chen

    (L.P. Markey Cancer Center, University of Kentucky)

  • Frank B. Gertler

    (Massachusetts Institute of Technology)

  • Michael D. Mendenhall

    (L.P. Markey Cancer Center, University of Kentucky)

  • Frank Sicheri

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
    University of Toronto)

  • Tony Pawson

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
    University of Toronto)

  • Mike Tyers

    (Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital
    University of Toronto)

Abstract

SCF ubiquitin ligases target phosphorylated substrates for ubiquitin-dependent proteolysis by means of adapter subunits called F-box proteins. The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an event necessary for the onset of DNA replication. The WD40 repeat domain of Cdc4 binds with high affinity to a consensus phosphopeptide motif (the Cdc4 phospho-degron, CPD), yet Sic1 itself has many sub-optimal CPD motifs that act in concert to mediate Cdc4 binding. The weak CPD sites in Sic1 establish a phosphorylation threshold that delays degradation in vivo, and thereby establishes a minimal G1 phase period needed to ensure proper DNA replication. Multisite phosphorylation may be a more general mechanism to set thresholds in regulated protein–protein interactions.

Suggested Citation

  • Piers Nash & Xiaojing Tang & Stephen Orlicky & Qinghua Chen & Frank B. Gertler & Michael D. Mendenhall & Frank Sicheri & Tony Pawson & Mike Tyers, 2001. "Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication," Nature, Nature, vol. 414(6863), pages 514-521, November.
    • Handle: RePEc:nat:nature:v:414:y:2001:i:6863:d:10.1038_35107009
    DOI: 10.1038/35107009
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35107009
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35107009?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Juan Manuel Valverde & Geronimo Dubra & Michael Phillips & Austin Haider & Carlos Elena-Real & Aurélie Fournet & Emile Alghoul & Dhanvantri Chahar & Nuria Andrés-Sanchez & Matteo Paloni & Pau Bernadó , 2023. "A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Jacob D Feala & Jorge Cortes & Phillip M Duxbury & Andrew D McCulloch & Carlo Piermarocchi & Giovanni Paternostro, 2012. "Statistical Properties and Robustness of Biological Controller-Target Networks," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-11, January.
    3. Maximilian Mosbacher & Sung Sik Lee & Gilad Yaakov & Mariona Nadal-Ribelles & Eulàlia Nadal & Frank Drogen & Francesc Posas & Matthias Peter & Manfred Claassen, 2023. "Positive feedback induces switch between distributive and processive phosphorylation of Hog1," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Anneke Brümmer & Carlos Salazar & Vittoria Zinzalla & Lilia Alberghina & Thomas Höfer, 2010. "Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication," PLOS Computational Biology, Public Library of Science, vol. 6(5), pages 1-13, May.
    5. Christopher A. Waudby & Saul Alvarez-Teijeiro & E. Josue Ruiz & Simon Suppinger & Nikos Pinotsis & Paul R. Brown & Axel Behrens & John Christodoulou & Anastasia Mylona, 2022. "An intrinsic temporal order of c-JUN N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:414:y:2001:i:6863:d:10.1038_35107009. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.