YAP1 gene

The YAP1 gene (YAP1 stands for: Yes1 Associated Transcriptional Regulator) is a protein-coding gene located on chromosome 11q22.1. Alternative splicing leads to several transcript variants encoding different isoforms. An important paralog of this gene is WWTR1.

The YAP1 gene encodes a downstream nuclear effector of the Hippo signaling pathway, which is involved in development, growth, repair and homeostasis. As a transcriptional regulator of this pathway, the YAP1 gene plays a role in the development and progression of various types of cancer and could serve as a potential target for cancer treatment.

The encoded protein is not a transcriptional regulator with a dual function as coactivator and co-repressor. It is critical for organ size control and tumor suppression by limiting proliferation and promoting apoptosis. The core of the Hippo signaling pathway comprises a kinase cascade with STK3/MST2 and STK4/MST1 and its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in conjunction with its regulatory protein MOB1. This activation leads to phosphorylation and inactivation of the oncoprotein YAP1 and WWTR1/TAZ (Zhao B et al. 2008). Phosphorylation of YAP1 by LATS1/2 prevents its translocation into the nucleus and thus regulates the expression of its target genes (Zhao B et al. 2008). Transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth and induction of epithelial-mesenchymal transition (EMT) ((Zhao B et al. 2008).

Plays a key role in tissue tension and 3D tissue structure by regulating the cortical actomyosin network and acting via ARHGAP18, a Rho GTPase-activating protein that suppresses F-actin polymerization (Porazinski S et al. 2015). It also suppresses ciliogenesis by acting as a transcriptional co-repressor of the TEAD4 target genes AURKA and PLK1.

Diseases associated with YAP1 include coloboma, ocular, with or without hearing impairment, cleft lip/palate and/or impaired mental development and uveal coloboma, cleft lip/palate and mental retardation. Associated signaling pathways include gene expression (transcription) and endothelial cell response to shear stress.

1. Porazinski S et al. (2015) YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature 521:217-221.
2. Rötzer V et al. (2016) Desmoglein 3-Dependent Signaling Regulates Keratinocyte Migration and Wound Healing. J Invest Dermatol 136:301-310.
3. Tsang SM et al. (2012) Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris. J Pathol 227:81-93.
4. Uttagomol J et al. (2019) Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces. Int J Mol Sci 20:6221.
5. Zhao B et al. (2008) TEAD mediates YAP-dependent gene induction and growth control. Genes Dev 22:1962-1971