title: The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase.
abstract: 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 β-TrCP and ubiquitylated by the SCF/CRL1(β-TrCP) E3 ligase. The interaction between TAZ and β-TrCP is regulated by the Hippo pathway. Phosphorylation of a phosphodegron in TAZ by LATS primes it for further phosphorylation by CK1ε and subsequent binding by β-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.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology School of Medicine.
authors.forename: Chen-Ying
authors.initials: CY
authors.lastname: Liu
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Zha
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Siew Wee
authors.initials: SW
authors.lastname: Chan
authors.forename: Chun Jye
authors.initials: CJ
authors.lastname: Lim
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Lei
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000818:Animals; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000099317:Hippo Kinases
chemical_list: D047389:Casein Kinase I; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D044843:SKP Cullin F-Box Protein Ligases; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C092745:LATS1 protein, human; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases