Figure 2.

The transcriptional co-activators YAP and TAZ are regulated by many cellular key players. Yes-associated protein (YAP) and its cellular homologue transcriptional co-activator with PDZ motif (TAZ) are master-regulators of cellular mechanotransduction. A plethora of upstream signals converge on these proteins. Nonetheless, there seems to be slight differences in the exact cellular functions of YAP and TAZ (details given in the main text). In the cytosol, YAP/TAZ are phosphorylated (P) and are bound by proteins from the 14-3-3 family, which prevent their translocation into the nucleus. YAP can additionally be bound by angiomotin (AMOT). Dephosphorylation of YAP/TAZ is mediated through regulators as diverse as focal adhesion kinase (FAK), cellular sarcoma (Src), coiled-coil-containing protein kinase 1 (ROCK), G-protein coupled receptors (GPCR), α-actinin, or the junctional proteins neurofibromatosis 2 (NF), KIBRA, and Salvador-homologue 1 (Sav1). RhoA also interacts with TAZ. In the nucleus, YAP may be trapped by zona occludens 2 (ZO-2) protein. Otherwise, YAP/TAZ interact with TEA domain family (TEAD) transcription factors to regulate gene expression. Genes written in green, such as cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), runt-related transcription factor 2 (RUNX2), osterix (OSX), osteopontin (OPN), ARMUS, collagen 1 (COL1), α-smooth muscle actin (α-SMA), cellular myelocytomatosis (c-myc), and cyclin D1 are upregulated by YAP/TAZ. Contrary to that, the pro-apoptotic B-cell lymphoma 2 (Bcl-2) as well as cyclin-dependent kinase inhibitor (CDKI) transcripts are downregulated by these transcriptional co-activators (yellow). Details are given in the main text.