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Malonia , S.K. and Yadav , B. and Sinha , S. and Lazennec , G. and Chattopadhyay , S. (2014) Chromatin remodeling protein SMAR1 regulates NF-κB dependent Interleukin-8 transcription in breast cancer. The International Journal of biochemistry and cell biology, 55. pp. 220-226.

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Abstract

Interleukin-8 (IL-8) is a pleiotropic chemokine involved in metastasis and angiogenesis of breast tumors. The expression of IL-8 is deregulated in metastatic breast carcinomas owing to aberrant NF-κB activity, which is known to positively regulate IL-8 transcription. Earlier, we have shown that tumor suppressor SMAR1 suppresses NF-κB transcriptional activity by modulating IκBα function. Here, we show that NF-κB target gene IL-8, is a direct transcriptional target of SMAR1. Using chromatin immunoprecipitation and reporter assays, we demonstrate that SMAR1 binds to IL-8 promoter MAR (matrix attachment region) and recruits HDAC1 dependent co-repressor complex. Further, we also show that SMAR1 antagonizes p300-mediated acetylation of RelA/p65, a post-translational modification indispensable for IL-8 transactivation. Thus, we decipher a new role of SMAR1 in NF-κB dependent transcriptional regulation of pro-angiogenic chemokine IL-8.

Item Type: Article
Subjects: Cancer Biology
Depositing User: Mr. Rameshwar Nema
Date Deposited: 27 May 2016 05:43
Last Modified: 27 May 2016 07:55
URI: http://nccs.sciencecentral.in/id/eprint/253

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