YAP1

Yes-associated protein 1 (YAP1) is a transcriptional co-activator that mediates gene expression downstream of the Hippo signaling pathway. In humans, the YAP1 gene encodes the YAP1 protein, which cannot bind DNA directly but functions by partnering with transcription factors such as TEAD1–4 to promote transcription of growth-related genes.

YAP1 activity is governed by the Hippo kinases MST1/2 and LATS1/2. When the Hippo pathway is active, LATS1/2 phosphorylate YAP1 at multiple sites, including serine 127, leading to binding by 14-3-3 proteins and cytoplasmic retention or degradation. When Hippo signaling is suppressed, YAP1 is dephosphorylated, accumulates in the nucleus, and co-activates transcription. In addition to Hippo regulation, YAP1 responds to mechanical cues, cell density, GPCR signaling, and energy stress, and it can interact with other signaling pathways such as Wnt and TGF-β/SMAD.

In the nucleus, YAP1 partners with TEAD transcription factors to drive expression of growth-promoting and anti-apoptotic genes. Principal target genes include CTGF and CYR61, among others. YAP1 can also interact with other transcriptional regulators such as SMADs, p73, and RUNX family members, enabling context-dependent effects on proliferation, differentiation, and cell survival.

Biological roles of YAP1 include organ size control during development, tissue regeneration, and stem cell maintenance. The activity of YAP1 is tightly regulated to maintain tissue homeostasis, and dysregulation—often through increased nuclear localization—has been linked to cancer progression and metastasis in various tissues.

Therapeutic interest surrounds strategies to inhibit YAP1 activity or disrupt YAP1-TEAD interactions, with several approaches under investigation in cancer research.