scholarly journals Positive and Negative Modulation of Vitamin D Receptor Function by Transforming Growth Factor-β Signaling through Smad Proteins

1999 ◽  
Vol 274 (19) ◽  
pp. 12971-12974 ◽  
Author(s):  
Yasuo Yanagi ◽  
Miyuki Suzawa ◽  
Masahiro Kawabata ◽  
Kohei Miyazono ◽  
Junn Yanagisawa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Vitamin D Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Function ◽  
Smad Proteins

scholarly journals Positive and negative modulation of vitamin D receptor function by transforming growth factor-β signaling through Smad proteins.

2013 ◽  
Vol 288 (42) ◽  
pp. 30504-30504
Author(s):  
Yasuo Yanagi ◽  
Miyuki Suzawa ◽  
Masahiro Kawabata ◽  
Kohei Miyazono ◽  
Junn Yanagisawa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Vitamin D Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Function ◽  
Smad Proteins

scholarly journals Relative Potencies of 1,25-(OH)2D3and 19-Nor-1,25-(OH)2D2on Inducing Differentiation and Markers of Bone Formation in MG-63 Cells

2001 ◽  
Vol 12 (7) ◽  
pp. 1468-1474
Author(s):  
JANE L. FINCH ◽  
ADRIANA S. DUSSO ◽  
TRICIA PAVLOPOULOS ◽  
EDUARDO A. SLATOPOLSKY
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Bone Formation ◽  
Cell Line ◽  
Vitamin D Receptor ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Antigen ◽  
Alp Activity

Abstract. 19-Nor-1,25-(OH)2D2, an analog of 1,25-(OH)2D3, is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)2D2is approximately 10 times less active than 1,25-(OH)2D3in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)2D2also could be less potent than 1,25-(OH)2D3on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-β, an enhancer of 1,25-(OH)2D3—induced ALP activity in this cell line. Transforming growth factor-β alone had no effect, whereas 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)2D2has the same potency as 1,25-(OH)2D3not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)2D2would have deleterious effects on bone remodeling.

Vitamin D receptor is involved in butyrate-induced transforming growth factor β-1 signaling in Caco-2 cells

2003 ◽  
Vol 124 (4) ◽  
pp. A280
Author(s):  
Tanja Gaschott ◽  
Oliver Schroeder ◽  
Dieter Steinhilber ◽  
Juergen Stein
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Vitamin D Receptor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Transforming Growth Factor β-Mediated Transcriptional Repression of c-myc Is Dependent on Direct Binding of Smad3 to a Novel Repressive Smad Binding Element

2004 ◽  
Vol 24 (6) ◽  
pp. 2546-2559 ◽  
Author(s):  
Joshua P. Frederick ◽  
Nicole T. Liberati ◽  
David S. Waddell ◽  
Yigong Shi ◽  
Xiao-Fan Wang
Keyword(s):  
Growth Factor ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Specific Cell ◽  
Smad Proteins ◽  
Smad Binding Element

ABSTRACT Smad proteins are the most well-characterized intracellular effectors of the transforming growth factor β (TGF-β) signal. The ability of the Smads to act as transcriptional activators via TGF-β-induced recruitment to Smad binding elements (SBE) within the promoters of TGF-β target genes has been firmly established. However, the elucidation of the molecular mechanisms involved in TGF-β-mediated transcriptional repression are only recently being uncovered. The proto-oncogene c-myc is repressed by TGF-β, and this repression is required for the manifestation of the TGF-β cytostatic program in specific cell types. We have shown that Smad3 is required for both TGF-β-induced repression of c-myc and subsequent growth arrest in keratinocytes. The transcriptional repression of c-myc is dependent on direct Smad3 binding to a novel Smad binding site, termed a repressive Smad binding element (RSBE), within the TGF-β inhibitory element (TIE) of the c-myc promoter. The c-myc TIE is a composite element, comprised of an overlapping RSBE and a consensus E2F site, that is capable of binding at least Smad3, Smad4, E2F-4, and p107. The RSBE is distinct from the previously defined SBE and may partially dictate, in conjunction with the promoter context of the overlapping E2F site, whether the Smad3-containing complex actively represses, as opposed to transactivates, the c-myc promoter.

The human NUPR1/P8 gene is transcriptionally activated by transforming growth factor β via the SMAD signalling pathway

2012 ◽  
Vol 445 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Roxane M. Pommier ◽  
Johann Gout ◽  
David F. Vincent ◽  
Carla E. Cano ◽  
Bastien Kaniewski ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Progression ◽  
Stress Resistance ◽  
Nuclear Protein ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transcriptional Level ◽  
Smad Proteins ◽  
Activation Cascade ◽  
Tgfβ Superfamily

NUPR1 (nuclear protein 1), also called P8 (molecular mass 8 kDa) or COM1 (candidate of metastasis 1), is involved in the stress response and in cancer progression. In the present study, we investigated whether human NUPR1 expression was regulated by TGFβ (transforming growth factor β), a secreted polypeptide largely involved in tumorigenesis. We demonstrate that the expression of NUPR1 was activated by TGFβ at the transcriptional level. We show that this activation is mediated by the SMAD proteins, which are transcription factors specifically involved in the signalling of TGFβ superfamily members. NUPR1 promoter analysis reveals the presence of a functional TGFβ-response element binding the SMAD proteins located in the genomic DNA region corresponding to the 5′-UTR (5′-untranslated region). Altogether, the molecular results of the present study, which demonstrate the existence of a TGFβ/SMAD/NUPR1 activation cascade, open the way to consider and investigate further a new mechanism enabling TGFβ to promote tumorigenesis by inducing stress resistance.

scholarly journals CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor β transcriptional responses in endothelial cells

1998 ◽  
Vol 95 (16) ◽  
pp. 9506-9511 ◽  
Author(s):  
James N. Topper ◽  
Maria R. DiChiara ◽  
Jonathan D. Brown ◽  
Amy J. Williams ◽  
Dean Falb ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Creb Binding Protein ◽  
Transcriptional Responses ◽  
Smad Proteins ◽  
Smad Protein

The transforming growth factor-β (TGF-β) superfamily of growth factors and cytokines has been implicated in a variety of physiological and developmental processes within the cardiovascular system. Smad proteins are a recently described family of intracellular signaling proteins that transduce signals in response to TGF-β superfamily ligands. We demonstrate by both a mammalian two-hybrid and a biochemical approach that human Smad2 and Smad4, two essential Smad proteins involved in mediating TGF-β transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator CREB binding protein (CBP). This interaction is specific in that it requires ligand (TGF-β) activation and is mediated by the transcriptional activation domains of the Smad proteins. A closely related, but distinct endothelial-expressed Smad protein, Smad7, which does not activate transcription in endothelial cells, does not interact with CBP. Furthermore, Smad2,4–CBP interactions involve the COOH terminus of CBP, a region that interacts with other regulated transcription factors such as certain signal transduction and transcription proteins and nuclear receptors. Smad–CBP interactions are required for Smad-dependent TGF-β-induced transcriptional responses in endothelial cells, as evidenced by inhibition with overexpressed 12S E1A protein and reversal of this inhibition with exogenous CBP. This report demonstrates a functional interaction between Smad proteins and an essential component of the mammalian transcriptional apparatus (CBP) and extends our insight into how Smad proteins may regulate transcriptional responses in many cell types. Thus, functional Smad–coactivator interactions may be an important locus of signal integration in endothelial cells.

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