TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities
Details
Publication Year 2022-12,Volume 8,Issue #12,Page 1033-1045
Journal Title
Trends in Cancer
Publication Type
Review
Abstract
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
Humans; *YAP-Signaling Proteins; Adaptor Proteins, Signal Transducing/genetics/metabolism; Phosphoproteins/genetics/chemistry/metabolism; Intracellular Signaling Peptides and Proteins; Trans-Activators/genetics/metabolism; Protein Serine-Threonine Kinases; Signal Transduction/genetics; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Transcription Factors/genetics/metabolism; *Neoplasms/drug therapy/genetics; Taz; TEAD transcription factors; Yap; chromatin remodeling; epigenetics; fusion proteins
Department(s)
Laboratory Research
PubMed ID
36096997
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