Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ.

YAP (yes-associated protein) and TAZ are oncogenic transcriptional co-activators downstream of the Hippo tumor-suppressor pathway. However, whether YAP and/or TAZ (YAP/TAZ) engage in transcriptional co-repression remains relatively unexplored. Here, we directly demonstrated that YAP/TAZ represses numerous target genes, including tumor-suppressor genes such as DDIT4 (DNA-damage-inducible transcript 4) and Trail (TNF-related apoptosis-inducing ligand). Mechanistically, the repressor function of YAP/TAZ requires TEAD (TEA domain) transcription factors. A YAP/TAZ-TEAD complex recruits the NuRD complex to deacetylate histones and alters nucleosome occupancy at target genes. Functionally, repression of DDIT4 and Trail by YAP/TAZ is required for mTORC1 (mechanistic target of rapamycin complex 1) activation and cell survival, respectively. Our demonstration of the transcriptional co-repressor activity of YAP/TAZ opens a new avenue for understanding the Hippo signaling pathway.

Kim M ，Kim T ，Johnson RL ，Lim DS ... -  《Cell Reports》

The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1.

Hansen CG ，Ng YL ，Lam WL ，Plouffe SW ，Guan KL ... -  《-》

A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ.

Tan G ，Cao X ，Dai Q ，Zhang B ，Huang J ，Xiong S ，Zhang Yy ，Chen W ，Yang J ，Li H ... -  《Oncotarget》

The novel YAP target gene, SGK1, upregulates TAZ activity by blocking GSK3β-mediated TAZ destabilization.

YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored. Here, we reveal that SGK1 is a potential positive feedback regulator of YAP and TAZ, showing that the TEAD-YAP/TAZ complex directly activates SGK1 transcription by binding to the distal enhancer of SGK1, and SGK1, in turn, stabilizes YAP/TAZ. Moreover, we demonstrate that expression of YAP/TAZ target genes is positively regulated by SGK1. Mechanistically, SGK1 inhibits ubiquitin-mediated degradation of TAZ by inhibiting GSK3β activity. These findings expand our understanding of YAP/TAZ regulation to include the novel downstream target of YAP, SGK1.

Yoo G ，Kim T ，Chung C ，Hwang DS ，Lim DS ... -  《-》

Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation.

Lin KC ，Moroishi T ，Meng Z ，Jeong HS ，Plouffe SW ，Sekido Y ，Han J ，Park HW ，Guan KL ... -  《-》