The novel YAP target gene, SGK1, upregulates TAZ activity by blocking GSK3 beta-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-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. (C) 2017 Elsevier Inc. All rights reserved.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Issue Date
2017-08
Language
English
Keywords

SIGNALING PATHWAY; HIPPO PATHWAY; GROWTH-FACTOR; SIZE-CONTROL; KINASE SGK; CANCER; INHIBITION; AKT; SERUM; DEGRADATION

Citation

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.490, no.3, pp.650 - 656

ISSN
0006-291X
DOI
10.1016/j.bbrc.2017.06.092
URI
http://hdl.handle.net/10203/225663
Appears in Collection
BS-Journal Papers(저널논문)
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