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Yes-associated protein

Yes-associated protein

Overview

Yes-associated protein (YAP) is a transcriptional coactivator and the principal downstream effector of the Hippo signaling pathway, a highly conserved kinase cascade that governs organ size, tissue homeostasis, and cellular proliferation. Originally identified as a binding partner of the Src-family kinase Yes, YAP lacks intrinsic DNA-binding activity and instead functions by partnering with transcription factors — most notably the TEAD family — to drive expression of genes promoting cell growth, survival, and stemness. Under conditions of active Hippo signaling, the kinases LATS1 and LATS2 phosphorylate YAP, triggering its cytoplasmic sequestration and proteasomal degradation. When upstream Hippo kinases are lost or suppressed, YAP accumulates in the nucleus and operates as an oncogenic driver across a broad spectrum of human malignancies.

Beyond its canonical role in the Hippo pathway, YAP functions as a mechanotransducer, sensing and relaying physical cues from the extracellular matrix (ECM) through integrin-mediated adhesion complexes and cytoskeletal tension. Its closely related paralog, TAZ (transcriptional coactivator with PDZ-binding motif), frequently acts in concert with YAP, and the two proteins are often studied together in the context of mechanobiology and cancer. YAP hyperactivation has been documented in uveal melanoma, glioblastoma, osteosarcoma, colorectal cancer, and numerous other solid tumors, positioning it as a high-priority therapeutic target in oncology.

Recent Publications Focus

Below is a summary of the newest research publications targeting Yes-associated protein (sorted by publication date).

  • PMID: 41980058 — cisplatin-Induced oxidative stress Regulates YAP to Modulate Epigenome Promoting the Survival of Osteosarcoma Cells.
    This study examined how cisplatin-induced oxidative stress influences YAP in osteosarcoma cells and how that, in turn, affects the epigenome and cell survival. The reported findings indicate that pharmacological inhibition or genetic ablation of YAP attenuated the cisplatin-induced accumulation of repressive chromatin marks, supporting a role for YAP in the stress-adaptive response of osteosarcoma cells. The work connects YAP with oxidative stress, cisplatin response, and epigenetic remodeling.

  • PMID: 41786044 — Intravitreal delivery of LATS1 mRNA by lipid nanoparticles as an effective strategy for uveal melanoma therapy.
    This publication focused on restoring upstream Hippo pathway control in uveal melanoma using intravitreal administration of LATS1 mRNA-loaded SM102-LNPs. The study describes YAP as a persistently activated oncogenic driver in uveal melanoma due to loss of upstream Hippo kinases, including LATS1. By delivering messenger RNA with lipid nanoparticles, the strategy aimed to re-establish LATS1 activity and thereby suppress YAP-driven signaling in an orthotopic UM mouse model. The work highlights YAP as a central therapeutic target in a setting of Hippo pathway deficiency.

  • PMID: 42003791 — Biodegradable Nickel Phosphide Mediated Adenosine Metabolism and Hippo Pathway Inhibition for Synergistic Photothermal Immunotherapy.
    This study investigated resveratrol-loaded and poly(acrylic acid)-coated biodegradable nickel phosphide nanoparticles in the context of adenosine metabolism and Hippo pathway modulation. The authors reported that increased adenosine can activate the Hippo signaling pathway for upregulating YAP expression and promoting tumor growth, making YAP relevant to the therapeutic mechanism being targeted. The work links YAP to a combined photothermal immunotherapy approach and to tumor-promoting signaling influenced by the microenvironment.

  • PMID: 42002768 — Biomimetic nanodecoys remodel the mechano-immune microenvironment to potentiate checkpoint blockade in colorectal cancer.
    This publication examined biomimetic nanodecoys designed to remodel the mechano-immune microenvironment in colorectal cancer and improve checkpoint inhibitor response. The study reported inhibition of the Integrin-FAK-YAP mechanotransduction axis, resulting in YAP cytoplasmic sequestration and reduced cytoskeletal tension. These findings place YAP at the center of a mechanical signaling program that can be therapeutically disrupted to alter tumor behavior and enhance immunotherapy.

  • PMID: 41936796 — Discovery and development of potent and selective dual NUAK/MARK inhibitors as Hippo pathway modulators for the treatment of cancer.
    This medicinal chemistry study developed dual NUAK/MARK inhibitors as modulators of the Hippo pathway. In the reported optimization process, inhibitor OICR19451 increased YAP phosphorylation and enhanced cytoplasmic YAP/TAZ localization, consistent with suppression of YAP transcriptional activity. The work supports the use of upstream kinase inhibition to control YAP localization and activity in cancer-relevant settings.

  • PMID: 41663008 — Inhibition of PRMT5-dependent YAP methylation attenuates tumorigenicity and radioresistance in glioblastoma.
    This study investigated PRMT5-dependent methylation of YAP in glioblastoma and its contribution to tumorigenicity and radioresistance. The authors describe YAP as a hyperactivated transcriptional coactivator downstream of the Hippo pathway implicated in glioblastoma initiation and progression. By targeting YAP methylation, the work suggests a mechanism through which YAP activity can be modulated to reduce malignant behavior and treatment resistance.

  • PMID: 41963941 — Smart hydrogels for overcoming cancer multidrug resistance.
    This review-like publication discussed smart hydrogels as a strategy to overcome multidrug resistance by first softening the extracellular matrix to decouple mechanotransduction driven by Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), and then disrupting hypoxia-driven bioenergetics. In this framework, YAP is presented as a mechanosensitive mediator linking matrix stiffness to drug resistance phenotypes. The article situates YAP within broader tumor microenvironment remodeling strategies, including injectable hydrogels and nanogel-enabled trafficking approaches.

Background PMIDs

  • [PMID 41663008]

Result PMIDs

  • [PMID 42003791]

Target PMIDs

  • [PMID 41936796]
  • [PMID 41980058]
  • [PMID 41786044]
  • [PMID 42003791]
  • [PMID 42002768]
  • [PMID 41963941]
Content is generated using Large Language Models (LLMs) and may contain errors or hallucinations. Experts periodically review it to verify accuracy and maintain database integrity.