A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF β-TRCP
University of California San Diego · Moores Cancer Center · +2 more institutions
Abstract
The Yes-associated protein (YAP) transcription coactivator is a key regulator of organ size and a candidate human oncogene. YAP is inhibited by the Hippo pathway kinase cascade, at least in part via phosphorylation of Ser 127, which results in YAP 14-3-3 binding and cytoplasmic retention. Here we report that YAP is phosphorylated by Lats on all of the five consensus HXRXXS motifs. Phosphorylation of Ser 381 in one of them primes YAP for subsequent phosphorylation by CK1delta/epsilon in a phosphodegron. The phosphorylated phosphodegron then recruits the SCF(beta-TRCP) E3 ubiquitin ligase, which catalyzes YAP ubiquitination, ultimately leading to YAP degradation. The phosphodegron-mediated degradation and the…
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Authors
5- BZBin ZhaoCorresponding
University of California San Diego, Moores Cancer Center
- LLLi Li
University of Michigan, University of California San Diego, Moores Cancer Center
- KTKaren Tumaneng
University of California San Diego, Moores Cancer Center
- CWCun‐Yu Wang
University of California, Los Angeles
- KGKun‐Liang Guan
University of California San Diego, Moores Cancer Center
Topics & keywords
- Phosphorylation
- Biology
- Ubiquitin ligase
- Cell biology
- Phosphorylation cascade
- Ubiquitin
- Hippo signaling pathway
- Coactivator