Cell type-dependent control of NF-Y activity by TGF-beta.

TY - JOUR

T1 - Cell type-dependent control of NF-Y activity by TGF-beta.

AU - Alabert, Constance

AU - Rogers, L

AU - Khan, L

AU - Niellez, S

AU - Fafet, P

AU - Cerulis, S

AU - Blanchard, J M

AU - Hipskind, R A

AU - Vignais, M-L

PY - 2006/6/8

Y1 - 2006/6/8

N2 - Transforming growth factor β (TGF-β) is a pluripotent cytokine that regulates cell growth and differentiation in a cell type-dependent fashion. TGF-β 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-β can also activate MAPK cascades. Here, we show that TGF-β 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-β-dependent transcriptional regulation of the NF-Y target gene cyclin A2. Interestingly, the kinetics of NF-YA relocalization differs between epithelial cells and fibroblasts. NIH3T3 fibroblasts show an elevated basal level of phosphorylated p38 and delayed nuclear accumulation of NF-YA after TGF-β 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-β1 involves ERK1/2 and potentially an interplay between MAPK pathways, thereby opening the possibility for finely tuned transcriptional regulation.

AB - Transforming growth factor β (TGF-β) is a pluripotent cytokine that regulates cell growth and differentiation in a cell type-dependent fashion. TGF-β 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-β can also activate MAPK cascades. Here, we show that TGF-β 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-β-dependent transcriptional regulation of the NF-Y target gene cyclin A2. Interestingly, the kinetics of NF-YA relocalization differs between epithelial cells and fibroblasts. NIH3T3 fibroblasts show an elevated basal level of phosphorylated p38 and delayed nuclear accumulation of NF-YA after TGF-β 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-β1 involves ERK1/2 and potentially an interplay between MAPK pathways, thereby opening the possibility for finely tuned transcriptional regulation.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-33745047111&origin=resultslist&sort=plf-f&src=s&sid=2c131cadd650e7a7c9d17352f61e6e7a&sot=b&sdt=b&s=TITLE%28Cell+type-dependent+control+of+NF-Y+activity+by+TGF-%CE%B2%29&sl=60&sessionSearchId=2c131cadd650e7a7c9d17352f61e6e7a&relpos=0

U2 - 10.1038/sj.onc.1209385

DO - 10.1038/sj.onc.1209385

M3 - Article

SN - 0950-9232

VL - 25

SP - 3387

EP - 3396

JO - Oncogene

JF - Oncogene

IS - 24

ER -