Transcriptional co-activator with PSD-95/Dlg-A/ZO-1 (PDZ)-binding motif (TAZ) regulates in cell proliferation and differentiation. In mesenchymal stem cells it promotes osteogenesis and myogenesis, and suppresses adipogenesis. TAZ activators are expected to prevent osteoporosis, obesity and muscle atrophy. TAZ activation induces epithelial-mesenchymal transition, confers stemness to cancer cells and leads to poor clinical prognosis in cancer patients. In this point of view, TAZ inhibitors should contribute to cancer therapy. Thus, TAZ attracts attention as a two-faced drug target. We screened for TAZ modulators by using human lung cancer A549 cells expressing the fluorescent reporter. Through this assay, we obtained TAZ activator candidates. We unexpectedly found that ethacridine, a widely used antiseptic and abortifacient, enhances the interaction of TAZ and protein phosphatases and increases unphosphorylated and nuclear TAZ. Ethacridine inhibits adipogenesis in mesenchymal C3H10T1/2 cells through the activation of TAZ. This finding suggests that ethacridine is a bona fide TAZ activator and supports that our assay is useful to discover TAZ activators.

Membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI)2 (also called synaptic scaffolding molecule (S-SCAM), atrophin-1-interacting protein 1, activin receptor-interacting protein 1) is a scaffold protein that binds a wide variety of receptors, cell adhesion molecules and signalling molecules. It also interacts with other scaffold proteins and adaptors, and forms a protein network that supports cell junctions. As it is highly expressed in brain, the study on its roles in synaptic organization initially preceded. However, mounting evidence indicates that MAGI2/S-SCAM functions as a tumour suppressor and plays essential roles to maintain the integrity of cell structures in non-neuronal tissues. We review the articles regarding to MAGI2/S-SCAM outside brain and discuss future perspectives for the research of MAGI family proteins.

Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them.

Yes-associated protein 1 (YAP1) was originally discovered as a WW domain-containing SRC kinase-binding protein. 1 YAP1 is distributed in the cytoplasm and in the nucleus. 2 YAP1 interacts with various transcription factors such as the TEAD family proteins, SMAD proteins, RUNX, and p73 to regulate gene transcription in the nucleus, while YAP1 undergoes proteasome degradation in the cytoplasm. [2][3][4][5][6][7] Therefore, cytoplasmic YAP1 is thought to be inactive, while nuclear YAP1 is considered to be active. The best characterized regulatory mechanism of the subcellular distribution of YAP1is its phosphorylation mediated by large tumor suppressor kinases (LATS1/2), the core kinases of the tumor suppressive Hippo pathway. LATS1/2 phosphorylate YAP1 at 5 serine residues. 2 The phosphorylation at

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