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Goal of this project is to elucidate the molecular determinants of the regulatory cross-talk that inflammatory pathways exert on steroid hormone genomic regulation. Tab2 is a component of the inflammatory pathway, and modulate response to various Transcription Factors by altering the coactivator/corepressor ratio at target genes, by displacing corepressor NCoR from transcriptional hubs. We reported that Tab2 interacts directly with Estrogen Receptor alpha and that constitutive activation of Tab2 confers Tamoxifen resistance to breast cancer cells by reversing the transcriptional response to many ERalpha-dependent genes (Cutrupi et al., 2012). In this project, we will 1) finely map the interaction of Tab2 with ERalpha and NCoR; 2) identify the mechanism of Tab2 activation and the proteins involved; 3) clarify the role of Tab2 in the genomic action of ERalpha in absence or presence of hormone, through genome wide transcription and chromatin occupancy studies.
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The call and how to apply are available at the following address: https://www.serviziweb.unito.it/albo_ateneo/
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