Transcriptional regulation of a metastasis suppressor gene by Tip60 and β-catenin complexes
- 14 April 2005
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 434 (7035), 921-926
- https://doi.org/10.1038/nature03452
Abstract
Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology because downregulation of tumour metastasis suppressor genes is a common occurrence1,2, and the underlying molecular mechanisms are not well established. Here we report that the downregulation of a metastasis suppressor gene, KAI1, in prostate cancer cells involves the inhibitory actions of β-catenin, along with a reptin chromatin remodelling complex. This inhibitory function of β-catenin–reptin requires both increased β-catenin expression and recruitment of histone deacetylase activity. The coordinated actions of β-catenin–reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex3,4,5,6,7,8 that is required for activation; the balance of these opposing complexes controls the expression of KAI1 and metastatic potential. The molecular mechanisms underlying the antagonistic regulation of β-catenin–reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-κB target genes.This publication has 20 references indexed in Scilit:
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