Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Although many studies reported mechanisms involved in the positive regulation of estrogens (E2) target genes, very little is known concerning the repressive effect of E2. In this study, we explored the molecular mechanisms by which E2 regulates CXCR7 expression in breast cancer cells. Our results show that E2-mediated down-regulation of CXCR7 occurs at the transcriptional level as demonstrated using actinomycin D and requires estrogen receptor alpha (ERα). In addition, CXCR7 is a primary ERα-target gene because the effect of E2 does not require the synthesis of an intermediary protein as revealed by the translational inhibitor cycloheximide treatment. Using an inhibitor of the NFκB pathway and chromatin immunoprecipitation assays, we demonstrated that NFκB is necessary for the high expression of CXCR7 gene and is recruited to the proximal promoter of the CXCR7 gene. Interestingly, the chromatin immunoprecipitation analyses also showed that E2-treatment significantly prevented the recruitment of NFκB to the promoter. Altogether, our results demonstrate that E2, through ERα, directly down-regulates CXCR7 expression by interfering with NFκB transcription factor at the promoter level.
ISSN: 0006-291X

inserm-00808966
http://www.hal.inserm.fr/inserm-00808966
DOI : 10.1016/j.bbrc.2013.01.050
PUBMED : 23352615

Éditeur(s) : HAL CCSD
Résumé : International audience
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin's extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin's ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees.
ISSN: 1934-6069

hal-01121777
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121777
PUBMED : 23159053
DOI : 10.1016/j.chom.2012.10.007
PUBMEDCENTRAL : PMC3556742