
pmid: 28634071
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.
Transcriptional Activation, Glycogen Synthase Kinase 3 beta, Protein Stability, Intracellular Signaling Peptides and Proteins, YAP-Signaling Proteins, Protein Serine-Threonine Kinases, Phosphoproteins, Cell Line, Immediate-Early Proteins, Up-Regulation, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Trans-Activators, Humans, Serum-Glucocorticoid Regulated Kinases, Adaptor Proteins, Signal Transducing, Transcription Factors
Transcriptional Activation, Glycogen Synthase Kinase 3 beta, Protein Stability, Intracellular Signaling Peptides and Proteins, YAP-Signaling Proteins, Protein Serine-Threonine Kinases, Phosphoproteins, Cell Line, Immediate-Early Proteins, Up-Regulation, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Trans-Activators, Humans, Serum-Glucocorticoid Regulated Kinases, Adaptor Proteins, Signal Transducing, Transcription Factors
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