Chromatin remodeling protein SMAR1 regulates NF-κB dependent Interleukin-8 transcription in breast cancer

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.
Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-02146532
Contributor : Gwendal Lazennec <>
Submitted on : Tuesday, June 4, 2019 - 9:33:24 AM
Last modification on : Thursday, August 1, 2019 - 2:14:02 PM

Identifiers

Collections

Citation

Sunil Malonia, Bhawna Yadav, Surajit Sinha, Gwendal Lazennec, Samit Chattopadhyay. Chromatin remodeling protein SMAR1 regulates NF-κB dependent Interleukin-8 transcription in breast cancer. The International Journal of Biochemistry & Cell Biology, 2014, 55, pp.220-226. ⟨10.1016/j.biocel.2014.09.008⟩. ⟨hal-02146532⟩

Share

Metrics

Record views

30