YAPTAZ

YAPTAZ refers to the two closely related transcriptional co-activators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, encoded by the WWTR1 gene) that function in mammals as key effectors of the Hippo signaling pathway. They do not bind DNA directly but regulate gene expression by partnering with transcription factors such as the TEAD family to promote transcription of genes involved in cell proliferation, survival, and stem cell maintenance. YAP and TAZ are essential for controlling organ size and tissue homeostasis in development and adulthood.

In cells, YAP and TAZ activity is governed by phosphorylation. When the Hippo pathway is active, LATS1/2 kinases phosphorylate YAP/TAZ, leading to binding of 14-3-3 proteins, cytoplasmic retention, and often proteasomal degradation. When the pathway is inactive, YAP and TAZ are dephosphorylated, accumulate in the nucleus, and cooperate with TEAD factors to activate target genes such as CTGF, CYR61, and others involved in growth and survival. Their localization and activity are influenced by mechanical cues, cell density, cytoskeletal tension, extracellular matrix stiffness, and various upstream signals including GPCR pathways and energy status.

YAP/TAZ play important roles in development, regeneration, and tissue homeostasis. Dysregulation and hyperactivation of YAP/TAZ have been linked to various cancers and fibrotic diseases, where they can promote proliferation, resistance to apoptosis, and invasive behavior. As a result, they are widely studied as potential targets for therapeutic intervention.