Nuclear AXIN2 represses MYC gene expression

Sherri A. Rennoll, Wesley M. Konsavage, Gregory Yochum

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The β-catenin transcriptional coactivator is the key mediator of the canonical Wnt signaling pathway. In the absence of Wnt, β-catenin associates with a cytosolic and multi-protein destruction complex where it is phosphorylated and targeted for proteasomal degradation. In the presence of Wnt, the destruction complex is inactivated and β-catenin translocates into the nucleus. In the nucleus, β-catenin binds T-cell factor (TCF) transcription factors to activate expression of c- MYC (MYC) and Axis inhibition protein 2 (AXIN2). AXIN2 is a member of the destruction complex and, thus, serves in a negative feedback loop to control Wnt/β-catenin signaling. AXIN2 is also present in the nucleus, but its function within this compartment is unknown. Here, we demonstrate that AXIN2 localizes to the nuclei of epithelial cells within normal and colonic tumor tissues as well as colorectal cancer cell lines. In the nucleus, AXIN2 represses expression of Wnt/β-catenin-responsive luciferase reporters and forms a complex with β-catenin and TCF. We demonstrate that AXIN2 co-occupies β-catenin/TCF complexes at the MYC promoter region. When constitutively localized to the nucleus, AXIN2 alters the chromatin structure at the MYC promoter and directly represses MYC gene expression. These findings suggest that nuclear AXIN2 functions as a rheostat to control MYC expression in response to Wnt/β-catenin signaling.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume443
Issue number1
DOIs
StatePublished - Jan 3 2014

Fingerprint

Catenins
Gene expression
Gene Expression
TCF Transcription Factors
Proteins
Wnt Signaling Pathway
Luciferases
Genetic Promoter Regions
Chromatin
Tumors
Colorectal Neoplasms
Transcription Factors
Epithelial Cells
Cells
Tissue
Feedback
Cell Line
Degradation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Rennoll, Sherri A. ; Konsavage, Wesley M. ; Yochum, Gregory. / Nuclear AXIN2 represses MYC gene expression. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 443, No. 1. pp. 217-222.
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Nuclear AXIN2 represses MYC gene expression. / Rennoll, Sherri A.; Konsavage, Wesley M.; Yochum, Gregory.

In: Biochemical and Biophysical Research Communications, Vol. 443, No. 1, 03.01.2014, p. 217-222.

Research output: Contribution to journalArticle

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