2. Academic Validation
  3. YAP condensates are highly organized hubs

YAP condensates are highly organized hubs

  • iScience. 2024 May 7;27(6):109927. doi: 10.1016/j.isci.2024.109927.
Siyuan Hao 1,  Ye Jin Lee 1,  Nadav Benhamou Goldfajn 1 2,  Eduardo Flores 3,  Jindayi Liang 1,  Hannah Fuehrer 1,  Justin Demmerle 1,  Jennifer Lippincott-Schwartz 4,  Zhe Liu 4,  Shahar Sukenik 3,  Danfeng Cai 1 5 6 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • 2 Department of Biophysics, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
  • 3 Department of Chemistry and Chemical Biology, University of California, Merced, Merced, CA 95343, USA.
  • 4 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
  • 5 Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • 6 Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
PMID: 38784009 DOI: 10.1016/j.isci.2024.109927
Abstract

YAP/TEAD signaling is essential for organismal development, cell proliferation, and Cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under Other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.

Keywords

Biophysics; molecular interaction; molecular mechanism of gene regulation; properties of biomolecules; protein.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-138565
    99.89%, YAP1/TAZ-TEAD Inhibitor
    YAP