TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities

Trends Cancer. 2022 Dec;8(12):1033-1045. doi: 10.1016/j.trecan.2022.08.002. Epub 2022 Sep 9.


The Hippo pathway is dysregulated in many different cancers, but point mutations in the pathway are rare. Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) fusion proteins have emerged in almost all major cancer types and represent the most common genetic mechanism by which the two transcriptional co-activators are activated. Given that the N termini of TAZ or YAP are fused to the C terminus of another transcriptional regulator, the resultant fusion proteins hyperactivate a TEAD transcription factor-based transcriptome. Recent advances show that the C-terminal fusion partners confer oncogenic properties to TAZ/YAP fusion proteins by recruiting epigenetic modifiers that promote a hybrid TEAD-based transcriptome. Elucidating these cooperating epigenetic complexes represents a strategy to identify new therapeutic approaches for a pathway that has been recalcitrant to medical therapy.

Keywords: TAZ; TEAD transcription factors; YAP; chromatin remodeling; epigenetics; fusion proteins.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases
  • Signal Transduction / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins*


  • YAP-Signaling Proteins
  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Intracellular Signaling Peptides and Proteins
  • Trans-Activators
  • Protein Serine-Threonine Kinases
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Transcription Factors