YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets

Mol Biol Rep. 2024 Dec 24;52(1):78. doi: 10.1007/s11033-024-10177-5.

Abstract

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key downstream effectors of the Hippo pathway that regulate organ size, tissue homeostasis, and cancer development. YAP/TAZ play crucial regulatory roles in organ growth, cell proliferation, cell renewal, and regeneration. Mechanistically, YAP/TAZ influence the occurrence and progression of liver regeneration (LR) through various signaling pathways, including Notch, Wnt/β-catenin, TGF-β/Smad. While the activation of YAP/TAZ can promote the regeneration of damaged liver tissue, their mechanisms of action may differ under various LR conditions. Furthermore, excessive activation of YAP/TAZ may also lead to severe liver damage, manifesting as alcoholic hepatitis, liver fibrosis, and even liver cancer. Here, we review the role and mechanisms of YAP/TAZ in LR and liver disease, highlighting the potential for advancements in clinical diagnosis and treatment targeting YAP/TAZ in these contexts.

Keywords: Liver disease; Liver regeneration; TAZ; YAP.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Regeneration* / physiology
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transcription Factors* / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / metabolism
  • YAP-Signaling Proteins* / metabolism

Substances

  • YAP-Signaling Proteins
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Adaptor Proteins, Signal Transducing
  • YAP1 protein, human
  • WWTR1 protein, human
  • Trans-Activators
  • Cell Cycle Proteins