The novel YAP target gene, SGK1, upregulates TAZ activity by blocking GSK3 beta-mediated TAZ destabilization

作者：Yoo Geon; Kim Tackhoon; Chung Chaeuk; Hwang Deog Su; Lim Dae Sik^*

来源：Biochemical and Biophysical Research Communications, 2017, 490(3): 650-656.

DOI：10.1016/j.bbrc.2017.06.092

• SGK1
• YAP
• TAZ
• Hippo pathway

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-YANTAZ 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 SGKl. Mechanistically, SGK1 inhibits ubiquitin-mediated degradation of TAZ by inhibiting GSK3 beta activity. These findings expand our understanding of YAP/TAZ regulation to include the novel downstream target of YAP, SGK1.

• 出版日期2017-8-26