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• W2117344319 endingPage "67" @default.
• W2117344319 startingPage "59" @default.
• W2117344319 abstract "Krüppel-like factor 5 (KLF5) is a PY motif-containing transcription factor promoting breast cell proliferation. The KLF5 protein is rapidly degraded through the proteasome after ubiquitination by E3 ubiquitin ligases, such as WWP1 and SCF Fbw7 . In this study, we demonstrated that a transcriptional co-activator with the PDZ-binding motif (TAZ) upregulated the KLF5 expression through antagonizing the WWP1-, but not Fbw7-, mediated KLF5 ubiquitination and degradation. TAZ interacted with KLF5 through the WW domain of TAZ and the PY motif of KLF5, which is the binding site for WWP1. TAZ inhibited WWP1–KLF5 protein interaction and WWP1-mediated KLF5 ubiquitination and degradation in a WW domain-dependent manner. Overexpression of TAZ upregulated the protein levels of KLF5 and FGF-BP, which is a well-established KLF5 target gene. In addition, depletion of TAZ in both 184A1 and HCC1937 breast cells downregulated protein levels of KLF5 and FGF-BP and inhibited cell growth. Furthermore, stable depletion of either TAZ or KLF5 significantly suppressed HCC1937 xenograft growth in immunodeficient mice. Knockdown of LATS1, a TAZ upstream inhibitory kinase, up-regulated the protein levels of KLF5 and FGF-BP in 184A1 and promoted cell growth through TAZ. Finally, both KLF5 and TAZ were co-expressed in a subset of estrogen receptor α-negative breast cell lines. These results, for the first time, suggest that TAZ promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5′s activities." @default.
• W2117344319 created "2016-06-24" @default.
• W2117344319 creator A5047917101 @default.
• W2117344319 creator A5052019890 @default.
• W2117344319 creator A5059927593 @default.
• W2117344319 creator A5085137414 @default.
• W2117344319 date "2011-10-31" @default.
• W2117344319 modified "2023-10-15" @default.
• W2117344319 title "TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis" @default.
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• W2117344319 doi "https://doi.org/10.1093/carcin/bgr242" @default.
• W2117344319 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22045023" @default.
• W2117344319 hasPublicationYear "2011" @default.
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