Table 1.

Biochemical, genetic, and cell fate-related differences between YAP and TAZ

Context/aspect	TAZ	YAP	Citation
Domain architecture	TEAD-binding, WW domain, coiled-coil, transactivation domain, PDZ binding (400 AAs)	Pro-rich, TEAD-binding, 1–2 WW domains, SH3-binding, coiled-coil, transactivation domain, PDZ binding (488 AAs)	[193]
Half-life	2 h in C3H/10T1/2 cells; < 1 h in U2OS cells	> 6 h in C3H/10T1/2 cells; ~ 1.5 h in U2OS cells	[107, 194]
Binding mode with TEAD	2:2 heterotetramer	1:1 heterodimer	[111, 195]
Self-dimerization	Yes	No (Murakami et al.), Yes for YAP2L isoform (Khanal et al.)	[114, 115]
Phase separation upon overexpression	Yes	No (Lu et al.), Yes (Cai et al.)	[113, 116]
Mutual regulation	TAZ does not affect YAP expression or stability (Finch-Edmondson et al.), knockdown of TAZ upregulates YAP (Muppala et al.)	YAP promotes TAZ degradation via GSK3 and HSP90	[109, 110]
Mouse embryonic null phenotype	Viable, but kidney disease present by E15.5 as well as lung defects, and post-natal survival is poor	Embryonic lethal between E9.5 and E10.5 with a shortened body axis, yolk sac vascular defect, caudal dysgenesis, and more	[26–29]
Mouse EpiSC and human ESC self-renewal	Sustains primed pluripotency by sequestering and stabilizing β-catenin in the cytoplasm; in hESCs, partners with OCT4 to repress mesendoderm genes	In hESCs, partners with OCT4 to repress mesendoderm genes; when overexpressed, promotes transition to naïve pluripotency	[44, 133, 196]
Osteogenesis in mesenchymal stem cells and periodontal ligament cells	Promotes osteogenesis and represses adipogenesis via binding with RUNX2, IRS-1, and/or Cbfα1	Promotes osteogenesis and represses adipogenesis by stabilizing nuclear β-catenin	[85, 124–127]
Early lung development	Promotes differentiation of alveolar type 1 cells, essential for lung regeneration via cell fate conversion of alveolar type 2 to type 1 cells	Suppresses Fgf10, enabling alveolar epithelial differentiation	[134, 135]
Corneal fibroblasts	Represses CTGF and αSMA, limiting YAP-mediated transdifferentiation via Smads	Activates CTGF and Smad2/3/4	[110]
T-cell differentiation	Prevents differentiation of T cells toward Treg cells and encourages TH17 helper T-cell differentiation	Inhibits differentiation of CD4 + T cells to TH1, TH17, TH2, and Treg fates and reduce tumor infiltration	[136, 137]
Myoblasts and mouse skeletal muscle tissues	Promotes myoblast proliferation, muscle growth, and myogenic differentiation, but not regeneration	Promotes myoblast proliferation and muscle regeneration, but not differentiation	[135]
Promoting apoptosis in cancer	Represses MYC and its targets in multiple myeloma	Binds to p73 and upregulates BAX in various cancer tissues	[142, 164, 165, 185, 197, 198]
Ferroptosis in cancer	Pro-ferroptotic via regulation of EMP1 in renal cell carcinoma or ANGPTL4 in ovarian cancer	Pro-ferroptotic via ACSL4 in colon cancer	[131, 186, 187]