Ligand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.
Bottom Line: We identified a novel interaction between ligand-dependent corepressor (LCoR) and the corepressor KRAB-associated protein-1 (KAP-1).We propose that ZBRK1, KAP-1 and LCoR form a transcriptional complex that silences gene expression, in particular FGF2, which maintains breast cell viability.Given the broad expression patterns of both LCoR and KAP-1 during development and in the adult, this complex may have several regulatory functions that extend beyond cell survival, mediated by interactions with ZBRK1 or other C2H2 zinc-finger proteins.
Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.Show MeSH
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Mentions: Previous studies revealed that increased levels of the secreted form of FGF2 reduce MCF-7 cell viability (21–23). As presented above, ablation of LCoR, KAP-1 or ZBRK1 did not lead to an apoptotic response in T47D cells, which do not express FGF2. To determine if increased FGF2 secretion resulted from ablation of ZBRK1, KAP-1 or LCoR in MCF-7 cells, we performed an ELISA for FGF2 in media supernatants. FGF2 secretion was enhanced about 4-fold 48 h after ablation of ZBRK1 or KAP-1, whereas another 24 h were necessary to further elevate (3-fold) FGF2 secretion after LCoR ablation (Figure 6A), consistent with delayed loss of LCoR expression (Supplementary Figure S5B).
Affiliation: Department of Physiology, McGill University, Montreal, QC, Canada.