| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
107-212 |
DRI_Background |
denotes |
Interleukin-8 (IL-8) is a pleiotropic chemokine involved in metastasis and angiogenesis of breast tumors. |
| T2 |
213-374 |
DRI_Background |
denotes |
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. |
| T3 |
375-496 |
DRI_Outcome |
denotes |
Earlier, we have shown that tumor suppressor SMAR1 suppresses NF-κB transcriptional activity by modulating IκBα function. |
| T4 |
497-584 |
DRI_Outcome |
denotes |
Here, we show that NF-κB target gene IL-8, is a direct transcriptional target of SMAR1. |
| T5 |
585-772 |
DRI_Approach |
denotes |
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. |
| T6 |
773-930 |
DRI_Outcome |
denotes |
Further, we also show that SMAR1 antagonizes p300-mediated acetylation of RelA/p65, a post-translational modification indispensable for IL-8 transactivation. |
| T7 |
931-1048 |
DRI_Approach |
denotes |
Thus, we decipher a new role of SMAR1 in NF-κB dependent transcriptional regulation of pro-angiogenic chemokine IL-8. |
