PMID- 20858893 OWN - NLM STAT- MEDLINE DCOM- 20101230 LR - 20211203 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 285 IP - 48 DP - 2010 Nov 26 TI - The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCFbeta-TrCP E3 ligase. PG - 37159-69 LID - 10.1074/jbc.M110.152942 [doi] AB - The TAZ transcription co-activator promotes cell proliferation and epithelial-mesenchymal transition. TAZ is inhibited by the Hippo tumor suppressor pathway, which promotes TAZ cytoplasmic localization by phosphorylation. We report here that TAZ protein stability is controlled by a phosphodegron recognized by the F-box protein beta-TrCP and ubiquitylated by the SCF/CRL1(beta-TrCP) E3 ligase. The interaction between TAZ and beta-TrCP is regulated by the Hippo pathway. Phosphorylation of a phosphodegron in TAZ by LATS primes it for further phosphorylation by CK1epsilon and subsequent binding by beta-TrCP. Therefore, the Hippo pathway negatively regulates TAZ function by both limiting its nuclear accumulation and promoting its degradation. The phosphodegron-mediated TAZ degradation plays an important role in negatively regulating TAZ biological functions. FAU - Liu, Chen-Ying AU - Liu CY AD - Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology School of Medicine. FAU - Zha, Zheng-Yu AU - Zha ZY FAU - Zhou, Xin AU - Zhou X FAU - Zhang, Heng AU - Zhang H FAU - Huang, Wei AU - Huang W FAU - Zhao, Di AU - Zhao D FAU - Li, Tingting AU - Li T FAU - Chan, Siew Wee AU - Chan SW FAU - Lim, Chun Jye AU - Lim CJ FAU - Hong, Wanjin AU - Hong W FAU - Zhao, Shimin AU - Zhao S FAU - Xiong, Yue AU - Xiong Y FAU - Lei, Qun-Ying AU - Lei QY FAU - Guan, Kun-Liang AU - Guan KL LA - eng GR - R01 CA132809/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100921 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Drosophila Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (Transcriptional Coactivator with PDZ-Binding Motif Proteins) RN - 0 (WWTR1 protein, human) RN - EC 2.3.2.27 (SKP Cullin F-Box Protein Ligases) RN - EC 2.7.1.- (LATS1 protein, human) RN - EC 2.7.11.1 (Casein Kinase I) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (hpo protein, Drosophila) SB - IM MH - Animals MH - Casein Kinase I/genetics/metabolism MH - Drosophila Proteins/genetics/metabolism MH - HEK293 Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism MH - Mice MH - NIH 3T3 Cells MH - Phosphorylation MH - Protein Binding MH - Protein Serine-Threonine Kinases/genetics/metabolism MH - Protein Stability MH - SKP Cullin F-Box Protein Ligases/genetics/*metabolism MH - *Signal Transduction MH - Trans-Activators MH - Transcription Factors MH - Transcriptional Coactivator with PDZ-Binding Motif Proteins PMC - PMC2988322 EDAT- 2010/09/23 06:00 MHDA- 2010/12/31 06:00 PMCR- 2011/11/26 CRDT- 2010/09/23 06:00 PHST- 2010/09/23 06:00 [entrez] PHST- 2010/09/23 06:00 [pubmed] PHST- 2010/12/31 06:00 [medline] PHST- 2011/11/26 00:00 [pmc-release] AID - S0021-9258(20)46692-X [pii] AID - M110.152942 [pii] AID - 10.1074/jbc.M110.152942 [doi] PST - ppublish SO - J Biol Chem. 2010 Nov 26;285(48):37159-69. doi: 10.1074/jbc.M110.152942. Epub 2010 Sep 21.