PUBLICATION
CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression
- Authors
- Park, S., Lee, M.S., Gwak, J., Choi, T.I., Lee, Y., Ju, B.G., Kim, C.H., Oh, S.
- ID
- ZDB-PUB-181005-4
- Date
- 2018
- Source
- Cell Death & Disease 9: 1023 (Journal)
- Registered Authors
- Kim, Cheol-Hee, Lee, Mi-Sun
- Keywords
- none
- MeSH Terms
-
- 3T3-L1 Cells
- Animals
- Axin Protein/metabolism*
- CCAAT-Enhancer-Binding Protein-beta/metabolism*
- Carcinoma, Hepatocellular/metabolism
- Cell Line
- Cell Proliferation/physiology
- Down-Regulation/physiology
- Drosophila
- Gene Expression/physiology*
- HEK293 Cells
- Humans
- Liver Neoplasms/metabolism
- Mice
- Signal Transduction/physiology*
- Wnt Signaling Pathway/physiology*
- Zebrafish
- beta Catenin/metabolism*
- PubMed
- 30283086 Full text @ Cell Death Dis.
Citation
Park, S., Lee, M.S., Gwak, J., Choi, T.I., Lee, Y., Ju, B.G., Kim, C.H., Oh, S. (2018) CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of AXIN1 gene expression. Cell Death & Disease. 9:1023.
Abstract
Axin1, a concentration-limiting component of the β-catenin destruction complex, negatively regulates the Wnt/β-catenin pathway. Axin1 concentration is reported to be regulated by proteasomal degradation; however, its transcriptional regulation has not yet been reported. Here, we demonstrated that CCAAT/enhancer-binding protein-β (C/EBP-β) activates axis inhibition protein 1 (AXIN1) gene expression, thereby attenuating Wnt/β-catenin signaling. C/EBP-β interacted with cis-regulatory element for C/EBP-β in the 5'-upstream sequences of the AXIN1 gene and increased AXIN1 promoter activity. Functional analysis using Drosophila and zebrafish models established that C/EBP-β negatively regulates the Wnt/β-catenin pathway. Small-molecule-based up-regulation of C/EBP-β induces AXIN1 gene expression and down-regulates the intracellular β-catenin level, thereby inhibiting hepatoma cell growth. Thus, our findings provide a unique mechanistic insight into the regulation of Axin homeostasis and present a novel strategy for the development of anticancer therapeutics targeting Wnt/β-catenin signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping