Yes-associated protein 1 (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ) (YAP1 (or YAP); TAZ (or WWTR1))

YAP (Yes-associated protein 1) and TAZ (Transcriptional coactivator with PDZ-binding motif) are closely related transcriptional coactivators that function as downstream effectors of the Hippo tumor suppressor pathway.[1][2][3] These proteins lack intrinsic DNA-binding domains and instead regulate gene expression by physically associating with DNA-binding transcription factors, most notably the TEAD family of transcription factors (TEAD1-4), to activate genes involved in cell proliferation, growth, and survival.[1][2] Their activity is regulated by Hippo pathway signaling: when the pathway is active, YAP/TAZ are phosphorylated and sequestered in the cytoplasm; when inactive, they translocate to the nucleus to act as transcriptional coactivators.[1][2][3] YAP and TAZ are frequently overexpressed and oncogenic in multiple cancer types including breast, lung, ovarian, colorectal, and prostate cancers, where they promote malignant proliferation, invasion, metastasis, and chemotherapy resistance.[1][3] However, these proteins also possess context-dependent tumor-suppressive functions when bound to different partner transcription factors such as p73, whereby they can induce apoptosis in response to DNA damage.[1] Currently, there are no FDA-approved drugs specifically targeting YAP/TAZ, but disrupting their interaction with TEAD transcription factors represents an active therapeutic strategy under development.[5]

Other names

Yes-associated proteinYAP65YAP1Transcriptional coactivator with PDZ-binding motifWWTR1

Acts as a transcriptional coactivator by binding to DNA-binding transcription factors (primarily TEAD family members) to regulate target gene expression. Lacks intrinsic DNA-binding activity and requires partner transcription factors. Regulated by the Hippo pathway through phosphorylation and cytoplasmic sequestration. Competitive inhibition of TEAD/VGLL4 repressor complexes. Recruitment of SWI/SNF complexes and chromatin remodelers via partner proteins.