IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37671-x.html
   My bibliography  Save this article

Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2

Author

Listed:
  • Rui Li

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Jingchen Shao

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Young-June Jin

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Haruya Kawase

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Yu Ting Ong

    (Angiogenesis & Metabolism Laboratory)

  • Kerstin Troidl

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology
    University Hospital Frankfurt and Wolfgang Goethe University Frankfurt)

  • Qi Quan

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Lei Wang

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Remy Bonnavion

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology)

  • Astrid Wietelmann

    (Small Animal Imaging Service Group)

  • Francoise Helmbacher

    (Aix Marseille Université, CNRS, IBDM UMR 7288, Parc Scientifique de Luminy, Case 907)

  • Michael Potente

    (Angiogenesis & Metabolism Laboratory
    Berlin Institute of Health at Charité—Universitätsmedizin Berlin, and Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Johannes Graumann

    (Max Planck Institute for Heart and Lung Research, Biomolecular Mass Spectrometry Service Group
    Philipps-University Marburg)

  • Nina Wettschureck

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology
    Goethe University Frankfurt
    Cardiopulmonary Institute
    German Center for Cardiovascular Research, Partner Site Frankfurt)

  • Stefan Offermanns

    (Max Planck Institute for Heart and Lung Research, Department of Pharmacology
    Goethe University Frankfurt
    Cardiopulmonary Institute
    German Center for Cardiovascular Research, Partner Site Frankfurt)

Abstract

Activation of endothelial YAP/TAZ signaling is crucial for physiological and pathological angiogenesis. The mechanisms of endothelial YAP/TAZ regulation are, however, incompletely understood. Here we report that the protocadherin FAT1 acts as a critical upstream regulator of endothelial YAP/TAZ which limits the activity of these transcriptional cofactors during developmental and tumor angiogenesis by promoting their degradation. We show that loss of endothelial FAT1 results in increased endothelial cell proliferation in vitro and in various angiogenesis models in vivo. This effect is due to perturbed YAP/TAZ protein degradation, leading to increased YAP/TAZ protein levels and expression of canonical YAP/TAZ target genes. We identify the E3 ubiquitin ligase Mind Bomb-2 (MIB2) as a FAT1-interacting protein mediating FAT1-induced YAP/TAZ ubiquitination and degradation. Loss of MIB2 expression in endothelial cells in vitro and in vivo recapitulates the effects of FAT1 depletion and causes decreased YAP/TAZ degradation and increased YAP/TAZ signaling. Our data identify a pivotal mechanism of YAP/TAZ regulation involving FAT1 and its associated E3 ligase MIB2, which is essential for YAP/TAZ-dependent angiogenesis.

Suggested Citation

  • Rui Li & Jingchen Shao & Young-June Jin & Haruya Kawase & Yu Ting Ong & Kerstin Troidl & Qi Quan & Lei Wang & Remy Bonnavion & Astrid Wietelmann & Francoise Helmbacher & Michael Potente & Johannes Gra, 2023. "Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37671-x
    DOI: 10.1038/s41467-023-37671-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37671-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-37671-x?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. Diana S Nascimento & Mariana Valente & Tiago Esteves & Maria de Fátima de Pina & Joana G Guedes & Ana Freire & Pedro Quelhas & Perpétua Pinto-do-Ó, 2011. "MIQuant – Semi-Automation of Infarct Size Assessment in Models of Cardiac Ischemic Injury," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-9, September.
    2. T. Azad & H. J. Janse van Rensburg & E. D. Lightbody & B. Neveu & A. Champagne & A. Ghaffari & V. R. Kay & Y. Hao & H. Shen & B. Yeung & B. A. Croy & K. L. Guan & F. Pouliot & J. Zhang & C. J. B. Nico, 2018. "A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    3. Nathan W. Pierce & Gary Kleiger & Shu-ou Shan & Raymond J. Deshaies, 2009. "Detection of sequential polyubiquitylation on a millisecond timescale," Nature, Nature, vol. 462(7273), pages 615-619, December.
    4. Li Wang & Jiang-Yun Luo & Bochuan Li & Xiao Yu Tian & Li-Jing Chen & Yuhong Huang & Jian Liu & Dan Deng & Chi Wai Lau & Song Wan & Ding Ai & King-Lun Kingston Mak & Ka Kui Tong & Kin Ming Kwan & Nanpi, 2016. "Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow," Nature, Nature, vol. 540(7634), pages 579-582, December.
    5. Daniel Martin & Maria S. Degese & Lynn Vitale-Cross & Ramiro Iglesias-Bartolome & Juan Luis Callejas Valera & Zhiyong Wang & Xiaodong Feng & Huwate Yeerna & Vachan Vadmal & Toshiro Moroishi & Rick F. , 2018. "Assembly and activation of the Hippo signalome by FAT1 tumor suppressor," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Fan Yao & Zhicheng Zhou & Jongchan Kim & Qinglei Hang & Zhenna Xiao & Baochau N. Ton & Liang Chang & Na Liu & Liyong Zeng & Wenqi Wang & Yumeng Wang & Peijing Zhang & Xiaoyu Hu & Xiaohua Su & Han Lian, 2018. "SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    7. Sirio Dupont & Leonardo Morsut & Mariaceleste Aragona & Elena Enzo & Stefano Giulitti & Michelangelo Cordenonsi & Francesca Zanconato & Jimmy Le Digabel & Mattia Forcato & Silvio Bicciato & Nicola Elv, 2011. "Role of YAP/TAZ in mechanotransduction," Nature, Nature, vol. 474(7350), pages 179-183, June.
    8. Hyun-Jung Choi & Haiying Zhang & Hongryeol Park & Kyu-Sung Choi & Heon-Woo Lee & Vijayendra Agrawal & Young-Myeong Kim & Young-Guen Kwon, 2015. "Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    9. Longyue L. Cao & Dario F. Riascos-Bernal & Prameladevi Chinnasamy & Charlene M. Dunaway & Rong Hou & Mario A. Pujato & Brian P. O’Rourke & Veronika Miskolci & Liang Guo & Louis Hodgson & Andras Fiser , 2016. "Control of mitochondrial function and cell growth by the atypical cadherin Fat1," Nature, Nature, vol. 539(7630), pages 575-578, November.
    10. Lei Wang & ShengPeng Wang & Yue Shi & Rui Li & Stefan Günther & Yu Ting Ong & Michael Potente & Zuyi Yuan & Enqi Liu & Stefan Offermanns, 2020. "YAP and TAZ protect against white adipocyte cell death during obesity," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    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. Aurore Claude-Taupin & Pierre Isnard & Alessia Bagattin & Nicolas Kuperwasser & Federica Roccio & Biagina Ruscica & Nicolas Goudin & Meriem Garfa-Traoré & Alice Regnier & Lisa Turinsky & Martine Burti, 2023. "The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Cheng-Hai Zhang & Yao Gao & Han-Hwa Hung & Zhu Zhuo & Alan J. Grodzinsky & Andrew B. Lassar, 2022. "Creb5 coordinates synovial joint formation with the genesis of articular cartilage," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. 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.
    4. Atanu Paul & Stefano Annunziato & Bo Lu & Tianliang Sun & Olivera Evrova & Lara Planas-Paz & Vanessa Orsini & Luigi M. Terracciano & Olga Charlat & Zinger Yang Loureiro & Lei Ji & Raffaella Zamponi & , 2022. "Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. María García-García & Sara Sánchez-Perales & Patricia Jarabo & Enrique Calvo & Trevor Huyton & Liran Fu & Sheung Chun Ng & Laura Sotodosos-Alonso & Jesús Vázquez & Sergio Casas-Tintó & Dirk Görlich & , 2022. "Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    7. Joseph G. Kern & Andrew M. Tilston-Lunel & Anthony Federico & Boting Ning & Amy Mueller & Grace B. Peppler & Eleni Stampouloglou & Nan Cheng & Randy L. Johnson & Marc E. Lenburg & Jennifer E. Beane & , 2022. "Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. Shuangshuang Wan & Kepeng Wang & Peihong Huang & Xian Guo & Wurui Liu & Yaocheng Li & Jingjing Zhang & Zhiyang Li & Jiacheng Song & Wenjing Yang & Xianzheng Zhang & Xianguang Ding & David Tai Leong & , 2024. "Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Kirstin Meyer & Nicholas C. Lammers & Lukasz J. Bugaj & Hernan G. Garcia & Orion D. Weiner, 2023. "Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. 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.
    11. 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.
    12. 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.
    13. Sujin Kang & Jaekyung Kim & Areum Park & Minsoo Koh & Wonji Shin & Gayoung Park & Taeyun A. Lee & Hyung Jin Kim & Heonjong Han & Yongbo Kim & Myung Kyung Choi & Jae Hyung Park & Eunhye Lee & Hyun-Soo , 2023. "TRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Carmen Oi Ning Leung & Yang Yang & Rainbow Wing Hei Leung & Karl Kam Hei So & Hai Jun Guo & Martina Mang Leng Lei & Gregory Kenneth Muliawan & Yuan Gao & Qian Qian Yu & Jing Ping Yun & Stephanie Ma & , 2023. "Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    15. Jianyu Ye & Fahong Li & Ting Hua & Kewei Ma & Jinyu Wang & Zixin Zhao & Zhongning Yang & Chen Luo & Ruohan Jia & Yaming Li & Menghan Hao & Jian Wu & Mengji Lu & Zhenghong Yuan & Jiming Zhang & Jielian, 2024. "Liver mechanosignaling as a natural anti-hepatitis B virus mechanism," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    16. Cornelis J. Boogerd & Ilaria Perini & Eirini Kyriakopoulou & Su Ji Han & Phit La & Britt Swaan & Jari B. Berkhout & Danielle Versteeg & Jantine Monshouwer-Kloots & Eva Rooij, 2023. "Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    17. Abdel Rahman Abdel Fattah & Niko Kolaitis & Katrien Daele & Brian Daza & Andika Gregorius Rustandi & Adrian Ranga, 2023. "Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. Robin M. Skory & Adam A. Moverley & Goli Ardestani & Yanina Alvarez & Ana Domingo-Muelas & Oz Pomp & Blake Hernandez & Piotr Tetlak & Stephanie Bissiere & Claudio D. Stern & Denny Sakkas & Nicolas Pla, 2023. "The nuclear lamina couples mechanical forces to cell fate in the preimplantation embryo via actin organization," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Jie Fang & Shivendra Singh & Changde Cheng & Sivaraman Natarajan & Heather Sheppard & Ahmed Abu-Zaid & Adam D. Durbin & Ha Won Lee & Qiong Wu & Jacob Steele & Jon P. Connelly & Hongjian Jin & Wenan Ch, 2023. "Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    20. Xun Huang & Xinmeng Li & Hongyu Shen & Yiheng Zhao & Zhao Zhou & Yushuang Wang & Jingfei Yao & Kaili Xue & Dongmei Wu & Yifu Qiu, 2023. "Transcriptional repression of beige fat innervation via a YAP/TAZ-S100B axis," Nature Communications, Nature, vol. 14(1), pages 1-19, 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_s41467-023-37671-x. 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.