Activation of Transforming Growth Factor-beta/Smad Signaling Reduces Aggregate Formation of Mislocalized TAR DNA Binding Protein-43 (P03.182)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P03.182-P03.182
Author(s):  
M. Nakamura ◽  
S. Kaneko ◽  
H. Ito ◽  
J.-i. Fujisawa ◽  
H. Kusaka
2012 ◽  
Vol 11 (4) ◽  
pp. 182-193 ◽  
Author(s):  
Masataka Nakamura ◽  
Satoshi Kaneko ◽  
Hidefumi Ito ◽  
Shiwen Jiang ◽  
Kengo Fujita ◽  
...  

1997 ◽  
Vol 17 (12) ◽  
pp. 7019-7028 ◽  
Author(s):  
J M Yingling ◽  
M B Datto ◽  
C Wong ◽  
J P Frederick ◽  
N T Liberati ◽  
...  

Members of the Smad family of proteins are thought to play important roles in transforming growth factor beta (TGF-beta)-mediated signal transduction. In response to TGF-beta, specific Smads become inducibly phosphorylated, form heteromers with Smad4, and undergo nuclear accumulation. In addition, overexpression of specific Smad combinations can mimic the transcriptional effect of TGF-beta on both the plasminogen activator inhibitor 1 (PAI-1) promoter and the reporter construct p3TP-Lux. Although these data suggest a role for Smads in regulating transcription, the precise nuclear function of these heteromeric Smad complexes remains largely unknown. Here we show that in Mv1Lu cells Smad3 and Smad4 form a TGF-beta-induced, phosphorylation-dependent, DNA binding complex that specifically recognizes a bipartite binding site within p3TP-Lux. Furthermore, we demonstrate that Smad4 itself is a DNA binding protein which recognizes the same sequence. Interestingly, mutations which eliminate the Smad DNA binding site do not interfere with either TGF-beta-dependent transcriptional activation or activation by Smad3/Smad4 cooverexpression. In contrast, mutation of adjacent AP1 sites within this context eliminates both TGF-beta-dependent transcriptional activation and activation in response to Smad3/Smad4 cooverexpression. Furthermore, concatemerized AP1 sites, in isolation, are activated by Smad3/Smad4 cooverexpression and, to a certain extent, by TGF-beta. Taken together, these data suggest that the Smad3/Smad4 complex has at least two separable nuclear functions: it forms a rapid, yet transient sequence-specific DNA binding complex, and it potentiates AP1-dependent transcriptional activation.


2015 ◽  
Vol 24 (14) ◽  
pp. 4024-4036 ◽  
Author(s):  
C.-T. Su ◽  
J.-W. Huang ◽  
C.-K. Chiang ◽  
E. C. Lawrence ◽  
K. L. Levine ◽  
...  

2017 ◽  
Vol 125 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Supawich Morkmued ◽  
Joseph Hemmerle ◽  
Eric Mathieu ◽  
Virginie Laugel-Haushalter ◽  
Branka Dabovic ◽  
...  

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