Cell type-dependent control of NF-Y activity by TGF-β

Abstract : Transforming growth factor b (TGF-b) is a pluripotent cytokine that regulates cell growth and differentiation in a cell type-dependent fashion. TGF-b exerts its effects through the activation of several signaling pathways. One involves membrane proximal events that lead to nuclear translocation of members of the Smad family of transcriptional regulators. TGF-b can also activate MAPK cascades. Here, we show that TGF-b induces nuclear translocation of the NF-YA subunit of the transcription factor NF-Y by a process that requires activation of the ERK cascade. This results in increased binding of endogenous NF-Y to chromatin and TGF-b-dependent transcriptional regulation of the NF-Y target gene cyclin A2. Interestingly, the kinetics of NF-YA relocalization differs between epithelial cells and fibro-blasts. NIH3T3 fibroblasts show an elevated basal level of phosphorylated p38 and delayed nuclear accumulation of NF-YA after TGF-b treatment. In contrast, MDCK cells show low basal p38 activation, higher basal ERK phosphorylation and more rapid localization of NF-YA after induction. Thus, NF-Y activation by TGF-b1 involves ERK1/2 and potentially an interplay between MAPK pathways, thereby opening the possibility for finely tuned transcriptional regulation.
Keywords : TGF-b NF-Y MAPK
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Constance Alabert, L Rogers, L Kahn, S Niellez, Patrick Fafet, et al.. Cell type-dependent control of NF-Y activity by TGF-β. Oncogene, Nature Publishing Group, 2006, 25 (24), pp.3387 - 3396. ⟨10.1038/sj.onc.1209385⟩. ⟨inserm-01855905⟩

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