Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes - PubMed (original) (raw)

. 2005 Apr 14;434(7035):921-6.

doi: 10.1038/nature03452.

Bogyou Kim, Ling Cai, Hee June Choi, Kenneth A Ohgi, Chris Tran, Charlie Chen, Chin Ha Chung, Otmar Huber, David W Rose, Charles L Sawyers, Michael G Rosenfeld, Sung Hee Baek

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Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes

Jung Hwa Kim et al. Nature. 2005.

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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 occurrence, 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 beta-catenin, along with a reptin chromatin remodelling complex. This inhibitory function of beta-catenin-reptin requires both increased beta-catenin expression and recruitment of histone deacetylase activity. The coordinated actions of beta-catenin-reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex 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 beta-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-kappaB target genes.

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