title: 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.
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Malonia
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
authors.forename: Bhawna
authors.initials: B
authors.lastname: Yadav
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune 411007, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Sinha
authors.affiliation: INSERM, U844, University of Montpellier, Montpellier F-34091, France.
authors.forename: Gwendel
authors.initials: G
authors.lastname: Lazennec
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune 411007, India. Electronic address: samit@nccs.res.in.
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000107:Acetylation; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016209:Interleukin-8 / Q000235:genetics*; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C417914:BANP protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: HDAC1; NF-κB; Repressor; SMAR1; Transcription