IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37064-0.html
   My bibliography  Save this article

PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1

Author

Listed:
  • Alessandro Poli

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Fabrizio A. Pennacchio

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Andrea Ghisleni

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Mariagrazia Gennaro

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Margaux Lecacheur

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Paulina Nastały

    (University of Gdańsk and Medical University of Gdańsk)

  • Michele Crestani

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Francesca M. Pramotton

    (EMPA-Materials Science and Technology
    Institute for Mechanical Systems, ETH)

  • Fabio Iannelli

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Galina Beznusenko

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Alexander A. Mironov

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Valeria Panzetta

    (University of Naples Federico II
    University of Naples Federico II
    Istituto Italiano di Tecnologia, IIT@CRIB)

  • Sabato Fusco

    (University of Molise)

  • Bhavwanti Sheth

    (University of Southampton)

  • Dimos Poulikakos

    (Institute for Mechanical Systems, ETH)

  • Aldo Ferrari

    (Institute for Mechanical Systems, ETH)

  • Nils Gauthier

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Paolo A. Netti

    (University of Naples Federico II
    University of Naples Federico II
    Istituto Italiano di Tecnologia, IIT@CRIB)

  • Nullin Divecha

    (University of Southampton)

  • Paolo Maiuri

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    University of Naples Federico II)

Abstract

Phosphatidylinositol-5-phosphate (PtdIns5P)−4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P to PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B is the one with more prominent nuclear localisation. Here, we unveil the role of PIP4K2B as a mechanoresponsive enzyme. PIP4K2B protein level strongly decreases in cells growing on soft substrates. Its direct silencing or pharmacological inhibition, mimicking cell response to softness, triggers a concomitant reduction of the epigenetic regulator UHRF1 and induces changes in nuclear polarity, nuclear envelope tension and chromatin compaction. This substantial rewiring of the nucleus mechanical state drives YAP cytoplasmic retention and impairment of its activity as transcriptional regulator, finally leading to defects in cell spreading and motility. Since YAP signalling is essential for initiation and growth of human malignancies, our data suggest that potential therapeutic approaches targeting PIP4K2B could be beneficial in the control of the altered mechanical properties of cancer cells.

Suggested Citation

  • Alessandro Poli & Fabrizio A. Pennacchio & Andrea Ghisleni & Mariagrazia Gennaro & Margaux Lecacheur & Paulina Nastały & Michele Crestani & Francesca M. Pramotton & Fabio Iannelli & Galina Beznusenko , 2023. "PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37064-0
    DOI: 10.1038/s41467-023-37064-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37064-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37064-0?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. Mayumi Kitagawa & Pei-Ju Liao & Kyung Hee Lee & Jasmine Wong & See Cheng Shang & Noriaki Minami & Oltea Sampetrean & Hideyuki Saya & Dai Lingyun & Nayana Prabhu & Go Ka Diam & Radoslaw Sobota & Andrea, 2017. "Dual blockade of the lipid kinase PIP4Ks and mitotic pathways leads to cancer-selective lethality," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Dean J. Procter & Colleen Furey & Arturo G. Garza-Gongora & Steven T. Kosak & Derek Walsh, 2020. "Cytoplasmic control of intranuclear polarity by human cytomegalovirus," Nature, Nature, vol. 587(7832), pages 109-114, November.
    3. Giorgia Nardone & Jorge Oliver-De La Cruz & Jan Vrbsky & Cecilia Martini & Jan Pribyl & Petr Skládal & Martin Pešl & Guido Caluori & Stefania Pagliari & Fabiana Martino & Zuzana Maceckova & Marian Haj, 2017. "YAP regulates cell mechanics by controlling focal adhesion assembly," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    4. Lucia E. Rameh & Kimberley F. Tolias & Brian C. Duckworth & Lewis C. Cantley, 1997. "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate," Nature, Nature, vol. 390(6656), pages 192-196, November.
    Full references (including those not matched with items on IDEAS)

    Citations

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


    Cited by:

    1. Andrea Ghisleni & Mayte Bonilla-Quintana & Michele Crestani & Zeno Lavagnino & Camilla Galli & Padmini Rangamani & Nils C. Gauthier, 2024. "Mechanically induced topological transition of spectrin regulates its distribution in the mammalian cell cortex," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Fabrizio A. Pennacchio & Alessandro Poli & Francesca Michela Pramotton & Stefania Lavore & Ilaria Rancati & Mario Cinquanta & Daan Vorselen & Elisabetta Prina & Orso Maria Romano & Aldo Ferrari & Matt, 2024. "N2FXm, a method for joint nuclear and cytoplasmic volume measurements, unravels the osmo-mechanical regulation of nuclear volume in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

    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. Zhao Wang & Jan Lauko & Amanda W. Kijas & Elliot P. Gilbert & Petri Turunen & Ramanathan Yegappan & Dongxiu Zou & Jitendra Mata & Alan E. Rowan, 2023. "Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jiayu Liu & Chuanrong Zhao & Xue Xiao & Aohan Li & Yueqi Liu & Jianan Zhao & Linwei Fan & Zhenhui Liang & Wei Pang & Weijuan Yao & Wei Li & Jing Zhou, 2023. "Endothelial discoidin domain receptor 1 senses flow to modulate YAP activation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Zheng Zhang & Baoyong Sha & Lingzhu Zhao & Huan Zhang & Jinteng Feng & Cheng Zhang & Lin Sun & Meiqing Luo & Bin Gao & Hui Guo & Zheng Wang & Feng Xu & Tian Jian Lu & Guy M. Genin & Min Lin, 2022. "Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Nathan Meade & Helen K. Toreev & Ram P. Chakrabarty & Charles R. Hesser & Chorong Park & Navdeep S. Chandel & Derek Walsh, 2023. "The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Robin Caire & Estelle Audoux & Mireille Thomas & Elisa Dalix & Aurélien Peyron & Killian Rodriguez & Nicola Pordone & Johann Guillemot & Yann Dickerscheit & Hubert Marotte & François Vandenesch & Fréd, 2022. "YAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Ana Sousa-Ortega & Javier Vázquez-Marín & Estefanía Sanabria-Reinoso & Jorge Corbacho & Rocío Polvillo & Alejandro Campoy-López & Lorena Buono & Felix Loosli & María Almuedo-Castillo & Juan R. Martíne, 2023. "A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Sara G. Romeo & Ilaria Secco & Edoardo Schneider & Christina M. Reumiller & Celio X. C. Santos & Anna Zoccarato & Vishal Musale & Aman Pooni & Xiaoke Yin & Konstantinos Theofilatos & Silvia Cellone Tr, 2023. "Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity," Nature Communications, Nature, vol. 14(1), pages 1-18, 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_s41467-023-37064-0. 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.