IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42049-0.html
   My bibliography  Save this article

A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation

Author

Listed:
  • Juan Manuel Valverde

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Geronimo Dubra

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Michael Phillips

    (University of Denver)

  • Austin Haider

    (University of Denver)

  • Carlos Elena-Real

    (CBS, CNRS, University of Montpellier, INSERM)

  • Aurélie Fournet

    (CBS, CNRS, University of Montpellier, INSERM)

  • Emile Alghoul

    (IGH, CNRS, University of Montpellier)

  • Dhanvantri Chahar

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Nuria Andrés-Sanchez

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Matteo Paloni

    (University of Denver)

  • Pau Bernadó

    (CBS, CNRS, University of Montpellier, INSERM)

  • Guido Mierlo

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Michiel Vermeulen

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Henk Toorn

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Albert J. R. Heck

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

  • Angelos Constantinou

    (IGH, CNRS, University of Montpellier)

  • Alessandro Barducci

    (CBS, CNRS, University of Montpellier, INSERM)

  • Kingshuk Ghosh

    (University of Denver
    University of Denver)

  • Nathalie Sibille

    (CBS, CNRS, University of Montpellier, INSERM)

  • Puck Knipscheer

    (Oncode Institute, Hubrecht Institute–KNAW and University Medical Center)

  • Liliana Krasinska

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Daniel Fisher

    (IGMM, CNRS, University of Montpellier, INSERM
    Equipe Labellisée LIGUE 2018, Ligue Nationale Contre le Cancer)

  • Maarten Altelaar

    (University of Utrecht, Utrecht
    Netherlands Proteomics Center)

Abstract

Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42049-0
    DOI: 10.1038/s41467-023-42049-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42049-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42049-0?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. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. 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.
    3. Marti Quevedo & Lize Meert & Mike R. Dekker & Dick H. W. Dekkers & Johannes H. Brandsma & Debbie L. C. Berg & Zeliha Ozgür & Wilfred F. J. van IJcken & Jeroen Demmers & Maarten Fornerod & Raymond A. P, 2019. "Mediator complex interaction partners organize the transcriptional network that defines neural stem cells," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Philip Zegerman & John F. X. Diffley, 2007. "Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast," Nature, Nature, vol. 445(7125), pages 281-285, January.
    5. Seiji Tanaka & Toshiko Umemori & Kazuyuki Hirai & Sachiko Muramatsu & Yoichiro Kamimura & Hiroyuki Araki, 2007. "CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast," Nature, Nature, vol. 445(7125), pages 328-332, January.
    6. Damien Coudreuse & Paul Nurse, 2010. "Driving the cell cycle with a minimal CDK control network," Nature, Nature, vol. 468(7327), pages 1074-1079, December.
    7. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    8. Marti Quevedo & Lize Meert & Mike R. Dekker & Dick H. W. Dekkers & Johannes H. Brandsma & Debbie L. C. Berg & Zeliha Ozgür & Wilfred F. J. van IJcken & Jeroen Demmers & Maarten Fornerod & Raymond A. P, 2019. "Publisher Correction: Mediator complex interaction partners organize the transcriptional network that defines neural stem cells," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    9. Souradeep Basu & Jessica Greenwood & Andrew W. Jones & Paul Nurse, 2022. "Core control principles of the eukaryotic cell cycle," Nature, Nature, vol. 607(7918), pages 381-386, July.
    10. Arpan Kumar Rai & Jia-Xuan Chen & Matthias Selbach & Lucas Pelkmans, 2018. "Kinase-controlled phase transition of membraneless organelles in mitosis," Nature, Nature, vol. 559(7713), pages 211-216, July.
    11. 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.
    12. Diana Mahdessian & Anthony J. Cesnik & Christian Gnann & Frida Danielsson & Lovisa Stenström & Muhammad Arif & Cheng Zhang & Trang Le & Fredric Johansson & Rutger Schutten & Anna Bäckström & Ulrika Ax, 2021. "Spatiotemporal dissection of the cell cycle with single-cell proteogenomics," Nature, Nature, vol. 590(7847), pages 649-654, February.
    13. Shunsuke F. Shimobayashi & Pierre Ronceray & David W. Sanders & Mikko P. Haataja & Clifford P. Brangwynne, 2021. "Nucleation landscape of biomolecular condensates," Nature, Nature, vol. 599(7885), pages 503-506, November.
    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. Lennart Enders & Marton Siklos & Jan Borggräfe & Stefan Gaussmann & Anna Koren & Monika Malik & Tatjana Tomek & Michael Schuster & Jiří Reiniš & Elisa Hahn & Andrea Rukavina & Andreas Reicher & Tamara, 2023. "Pharmacological perturbation of the phase-separating protein SMNDC1," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Matthew Day & Bilal Tetik & Milena Parlak & Yasser Almeida-Hernández & Markus Räschle & Farnusch Kaschani & Heike Siegert & Anika Marko & Elsa Sanchez-Garcia & Markus Kaiser & Isabel A. Barker & Laure, 2024. "TopBP1 utilises a bipartite GINS binding mode to support genome replication," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative AI," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, National Bureau of Economic Research, Inc.
    4. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Shuo-Shuo Liu & Tian-Xia Jiang & Fan Bu & Ji-Lan Zhao & Guang-Fei Wang & Guo-Heng Yang & Jie-Yan Kong & Yun-Fan Qie & Pei Wen & Li-Bin Fan & Ning-Ning Li & Ning Gao & Xiao-Bo Qiu, 2024. "Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Xiaoke Yang & Mingqi Zhu & Xue Lu & Yuxin Wang & Junyu Xiao, 2024. "Architecture and activation of human muscle phosphorylase kinase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Efren Garcia-Maldonado & Andrew D. Huber & Sergio C. Chai & Stanley Nithianantham & Yongtao Li & Jing Wu & Shyaron Poudel & Darcie J. Miller & Jayaraman Seetharaman & Taosheng Chen, 2024. "Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Kristy Rochon & Brianna L. Bauer & Nathaniel A. Roethler & Yuli Buckley & Chih-Chia Su & Wei Huang & Rajesh Ramachandran & Maria S. K. Stoll & Edward W. Yu & Derek J. Taylor & Jason A. Mears, 2024. "Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    10. Katherine A. Ray & Joshua D. Lutgens & Ramesh Bista & Jie Zhang & Ronak R. Desai & Melissa Hirsch & Takeshi Miyazawa & Antonio Cordova & Adrian T. Keatinge-Clay, 2024. "Assessing and harnessing updated polyketide synthase modules through combinatorial engineering," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Fan Lu & Liang Zhu & Thomas Bromberger & Jun Yang & Qiannan Yang & Jianmin Liu & Edward F. Plow & Markus Moser & Jun Qin, 2022. "Mechanism of integrin activation by talin and its cooperation with kindlin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    12. Zengyu Shao & Jiuwei Lu & Nelli Khudaverdyan & Jikui Song, 2024. "Multi-layered heterochromatin interaction as a switch for DIM2-mediated DNA methylation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Yudong Gao & Daichi Shonai & Matthew Trn & Jieqing Zhao & Erik J. Soderblom & S. Alexandra Garcia-Moreno & Charles A. Gersbach & William C. Wetsel & Geraldine Dawson & Dmitry Velmeshev & Yong-hui Jian, 2024. "Proximity analysis of native proteomes reveals phenotypic modifiers in a mouse model of autism and related neurodevelopmental conditions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Martin F. Peter & Christian Gebhardt & Rebecca Mächtel & Gabriel G. Moya Muñoz & Janin Glaenzer & Alessandra Narducci & Gavin H. Thomas & Thorben Cordes & Gregor Hagelueken, 2022. "Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Jutta Diessl & Jens Berndtsson & Filomena Broeskamp & Lukas Habernig & Verena Kohler & Carmela Vazquez-Calvo & Arpita Nandy & Carlotta Peselj & Sofia Drobysheva & Ludovic Pelosi & F.-Nora Vögtle & Fab, 2022. "Manganese-driven CoQ deficiency," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. Alexander Kroll & Sahasra Ranjan & Martin K. M. Engqvist & Martin J. Lercher, 2023. "A general model to predict small molecule substrates of enzymes based on machine and deep learning," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Lisa-Marie Appel & Vedran Franke & Johannes Benedum & Irina Grishkovskaya & Xué Strobl & Anton Polyansky & Gregor Ammann & Sebastian Platzer & Andrea Neudolt & Anna Wunder & Lena Walch & Stefanie Kais, 2023. "The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    18. Maciej K. Kocylowski & Hande Aypek & Wolfgang Bildl & Martin Helmstädter & Philipp Trachte & Bernhard Dumoulin & Sina Wittösch & Lukas Kühne & Ute Aukschun & Carolin Teetzen & Oliver Kretz & Botond Ga, 2022. "A slit-diaphragm-associated protein network for dynamic control of renal filtration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    19. Susan Kilgas & Aleem Syed & Patrick Toolan-Kerr & Michelle L. Swift & Shrabasti Roychoudhury & Aniruddha Sarkar & Sarah Wilkins & Mikayla Quigley & Anna R. Poetsch & Maria Victoria Botuyan & Gaofeng C, 2024. "NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Marie C. Schoelmerich & Lynn Ly & Jacob West-Roberts & Ling-Dong Shi & Cong Shen & Nikhil S. Malvankar & Najwa Taib & Simonetta Gribaldo & Ben J. Woodcroft & Christopher W. Schadt & Basem Al-Shayeb & , 2024. "Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires," Nature Communications, Nature, vol. 15(1), pages 1-17, 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_s41467-023-42049-0. 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.