Tumor suppressor SMAR1 downregulates Cytokeratin 8 expression by displacing p53 from its cognate site.

Abstract	Intermediary filaments play a crucial role in transformation of cells to a malignant phenotype. Here, we report that tumor suppressor SMAR1 downregulates Cytokeratin 8 gene expression by modulating p53-mediated transactivation of this gene. Moreover, the cell surface cytokeratin expression was downregulated leading to a decreased migration and invasiveness of cells. We further validated these results using genotoxic stress agents that lead to an increase in the levels of SMAR1 protein. This subsequently represses the transcription of Cytokeratin 8 gene by local chromatin condensation mediated by histone methylation and deacetylation. Evaluation of SMAR1 and Cytokeratin 8 proteins in different grades of cancer using tissue microarray point out at the inverse expression profiles of these genes (i.e. low levels of SMAR1 correlating with high expression of Cytokeratin 8) in higher grades of breast cancer. Therefore, the results presented here highlight the mechanism of Cytokeratin 8 gene regulation by interplay of tumor suppressor proteins SMAR1 and p53.
Authors	Lakshminarasimhan Pavithra, Sandeep Singh, Kadreppa Sreenath, Samit Chattopadhyay
Journal	The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 41 Issue 4 Pg. 862-71 (Apr 2009) ISSN: 1878-5875 [Electronic] Netherlands
PMID	18822384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BANP protein, human Cell Cycle Proteins Chromatin DNA-Binding Proteins Keratin-8 Nuclear Proteins Tumor Suppressor Protein p53
Topics	Adenocarcinoma (genetics, metabolism) Breast Neoplasms (genetics, metabolism) Cell Cycle Proteins (genetics, metabolism) Cell Line, Tumor Chromatin (metabolism) DNA Damage DNA-Binding Proteins (genetics, metabolism) Down-Regulation Gene Expression Regulation, Neoplastic Humans Immunoblotting Immunoprecipitation Keratin-8 (biosynthesis, genetics) Lung Neoplasms (genetics, metabolism) Nuclear Proteins (genetics, metabolism) Reverse Transcriptase Polymerase Chain Reaction Transfection Tumor Suppressor Protein p53 (genetics, metabolism)

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