IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36035-9.html
   My bibliography  Save this article

Phosphosite Scanning reveals a complex phosphorylation code underlying CDK-dependent activation of Hcm1

Author

Listed:
  • Michelle M. Conti

    (University of Massachusetts Chan Medical School)

  • Rui Li

    (University of Massachusetts Chan Medical School)

  • Michelle A. Narváez Ramos

    (University of Massachusetts Chan Medical School)

  • Lihua Julie Zhu

    (University of Massachusetts Chan Medical School
    University of Massachusetts Chan Medical School)

  • Thomas G. Fazzio

    (University of Massachusetts Chan Medical School)

  • Jennifer A. Benanti

    (University of Massachusetts Chan Medical School)

Abstract

Ordered cell cycle progression is coordinated by cyclin dependent kinases (CDKs). CDKs often phosphorylate substrates at multiple sites clustered within disordered regions. However, for most substrates, it is not known which phosphosites are functionally important. We developed a high-throughput approach, Phosphosite Scanning, that tests the importance of each phosphosite within a multisite phosphorylated domain. We show that Phosphosite Scanning identifies multiple combinations of phosphosites that can regulate protein function and reveals specific phosphorylations that are required for phosphorylation at additional sites within a domain. We applied this approach to the yeast transcription factor Hcm1, a conserved regulator of mitotic genes that is critical for accurate chromosome segregation. Phosphosite Scanning revealed a complex CDK-regulatory circuit that mediates Cks1-dependent phosphorylation of key activating sites in vivo. These results illuminate the mechanism of Hcm1 activation by CDK and establish Phosphosite Scanning as a powerful tool for decoding multisite phosphorylated domains.

Suggested Citation

  • Michelle M. Conti & Rui Li & Michelle A. Narváez Ramos & Lihua Julie Zhu & Thomas G. Fazzio & Jennifer A. Benanti, 2023. "Phosphosite Scanning reveals a complex phosphorylation code underlying CDK-dependent activation of Hcm1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36035-9
    DOI: 10.1038/s41467-023-36035-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36035-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36035-9?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
    ---><---

    References listed on IDEAS

    as
    1. Jeffrey A. Ubersax & Erika L. Woodbury & Phuong N. Quang & Maria Paraz & Justin D. Blethrow & Kavita Shah & Kevan M. Shokat & David O. Morgan, 2003. "Targets of the cyclin-dependent kinase Cdk1," Nature, Nature, vol. 425(6960), pages 859-864, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Emily N Manderson & Mohan Malleshaiah & Stephen W Michnick, 2008. "A Novel Genetic Screen Implicates Elm1 in the Inactivation of the Yeast Transcription Factor SBF," PLOS ONE, Public Library of Science, vol. 3(1), pages 1-9, January.
    2. 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.

    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:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36035-9. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.