9295299

pubmed:Citation

38

Transforming growth factor beta (TGF-beta) is a pluripotent peptide hormone that regulates various cellular activities, including growth, differentiation, and extracellular matrix protein gene expression. We previously showed that TGF-beta induces the transcriptional activation domain (TAD) of CTF-1, the prototypic member of the CTF/NF-I family of transcription factors. This induction correlates with the proposed role of CTF/NF-I binding sites in collagen gene induction by TGF-beta. However, the mechanisms of TGF-beta signal transduction remain poorly understood. Here, we analyzed the role of free calcium signaling in the induction of CTF-1 transcriptional activity by TGF-beta. We found that TGF-beta stimulates calcium influx and mediates an increase of the cytoplasmic calcium concentration in NIH3T3 cells. TGF-beta induction of CTF-1 is inhibited in cells pretreated with thapsigargin, which depletes the endoplasmic reticulum calcium stores, thus further arguing for the potential relevance of calcium mobilization in TGF-beta action. Consistent with this possibility, expression of a constitutively active form of the calcium/calmodulin-dependent phosphatase calcineurin or of the calcium/calmodulin-dependent kinase IV (DeltaCaMKIV) specifically induces the CTF-1 TAD and the endogenous mouse CTF/NF-I proteins. Both calcineurin- and DeltaCaMKIV-mediated induction require the previously identified TGF-beta-responsive domain of CTF-1. The immunosuppressants cyclosporin A and FK506 abolish calcineurin-mediated induction of CTF-1 activity. However, TGF-beta still induces the CTF-1 TAD in cells treated with these compounds or in cells overexpressing both calcineurin and DeltaCaMKIV, suggesting that other calcium-sensitive enzymes might mediate TGF-beta action. These results identify CTF/NF-I as a novel calcium signaling pathway-responsive transcription factor and further suggest multiple molecular mechanisms for the induction of CTF/NF-I transcriptional activity by growth factors.

http://linkedlifedata.com/resource/pubmed/journal/2985121R

http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/CTF-1 transcription factor, http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Camk4 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NFI Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta

Sep

pubmed-author:AlevizopoulosAA, pubmed-author:DusserreYY, pubmed-author:MermodNN, pubmed-author:RüeggUU

19

NLM

23597-605

pubmed-meshheading:9295299-3T3 Cells, pubmed-meshheading:9295299-Animals, pubmed-meshheading:9295299-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:9295299-Calcineurin, pubmed-meshheading:9295299-Calcium, pubmed-meshheading:9295299-Calcium-Calmodulin-Dependent Protein Kinase Type 4, pubmed-meshheading:9295299-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:9295299-Calmodulin-Binding Proteins, pubmed-meshheading:9295299-Cyclosporine, pubmed-meshheading:9295299-DNA-Binding Proteins, pubmed-meshheading:9295299-Mice, pubmed-meshheading:9295299-NFI Transcription Factors, pubmed-meshheading:9295299-Phosphoprotein Phosphatases, pubmed-meshheading:9295299-Signal Transduction, pubmed-meshheading:9295299-Tacrolimus, pubmed-meshheading:9295299-Transcription Factors, pubmed-meshheading:9295299-Transcriptional Activation, pubmed-meshheading:9295299-Transforming Growth Factor beta

Regulation of the transforming growth factor beta-responsive transcription factor CTF-1 by calcineurin and calcium/calmodulin-dependent protein kinase IV.

Journal Article