PMID- 10559222
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 47
DP  - 1999 Nov 19
TI  - Regulation of Smad7 promoter by direct association with Smad3 and Smad4.
PG  - 33412-8
AB  - Smad7 is a regulatory Smad protein that is able to antagonize signal transduction
      by transforming growth factor-beta (TGF-beta) and activin receptors. To
      characterize the regulation of Smad7 at the transcriptional level, we isolated
      the promoter region of the mouse Smad7 gene. When the Smad7 promoter luciferase
      reporter gene (-408 and +112 bp) was expressed in human hepatoma (HepG2) cells,
      its transcriptional activity was increased following TGF-beta or activin
      treatment. In addition, this region of the Smad7 promoter was stimulated by
      ectopic expression of Smad3 as well as constitutively active TGF-beta and activin
      receptors, indicating that Smad7 transcription was modulated by the signaling
      downstream those two receptors. A gel mobility shift assay indicated that a DNA
      fragment spanning -408 to -126 base pairs (bp) was able to directly bind purified
      Smad4. Furthermore, a consensus Smad3-Smad4 binding element (SBE) was discovered 
      in this region of the promoter with a palindromic sequence of GTCTAGAC. A 33-bp
      Smad7 promoter fragment containing this SBE was able to bind Smad3 and Smad4. In 
      human embryonic kidney 293 cells, the expression of constitutively active
      TGF-beta type I receptor was able to induce the formation of a Smad3- and
      Smad4-containing nuclear protein complex that bound the SBE. In HepG2 cells,
      TGF-beta1 treatment could induce the formation of an endogenous SBE-binding
      complex. Taken together, these data provided the first evidence that Smad7
      transcription is regulated by TGF-beta and activin signaling through direct
      binding of Smad3 and Smad4 to the Smad7 promoter.
FAU - Nagarajan, R P
AU  - Nagarajan RP
AD  - Department of Medical Genetics, Walther Oncology Center, Indiana University
      School of Medicine, Indianapolis, Indiana 46202, USA.
FAU - Zhang, J
AU  - Zhang J
FAU - Li, W
AU  - Li W
FAU - Chen, Y
AU  - Chen Y
LA  - eng
SI  - GENBANK/AF167314
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (SMAD4 protein, human)
RN  - 0 (SMAD7 protein, human)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, mouse)
RN  - 0 (Smad4 Protein)
RN  - 0 (Smad4 protein, mouse)
RN  - 0 (Smad7 Protein)
RN  - 0 (Smad7 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 104625-48-1 (Activins)
RN  - 57285-09-3 (Inhibins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Activins
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA
MH  - DNA-Binding Proteins/*genetics/*metabolism
MH  - Humans
MH  - Inhibins/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Promoter Regions, Genetic
MH  - Protein Binding
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Smad3 Protein
MH  - Smad4 Protein
MH  - Smad7 Protein
MH  - Trans-Activators/*genetics/*metabolism
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/metabolism
MH  - Tumor Cells, Cultured
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1074/jbc.274.47.33412 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 19;274(47):33412-8. doi: 10.1074/jbc.274.47.33412.