scholarly journals 214. Dominant-Negative Interference in the Pahenu2 Mouse: Modified Forms of PAH

2006 ◽  
Vol 13 ◽  
pp. S82-S83
Author(s):  
Andreas Zori ◽  
Dawn D. Yang ◽  
Jon-Michael Knapp ◽  
Catherine E. Charron ◽  
Jennifer E. Embury ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Negative Interference ◽  
Dominant Negative Interference ◽  
Modified Forms

scholarly journals Dominant‐negative interference with defence signalling by truncation mutations of the tomato Cf‐9 disease resistance gene

2006 ◽  
Vol 46 (3) ◽  
pp. 385-399 ◽  
Author(s):  
Claire L. Barker ◽  
Brett K. Baillie ◽  
Kim E. Hammond‐Kosack ◽  
Jonathan D. G. Jones ◽  
David A. Jones
Keyword(s):  
Disease Resistance ◽  
Resistance Gene ◽  
Dominant Negative ◽  
Disease Resistance Gene ◽  
Negative Interference ◽  
Defence Signalling ◽  
Dominant Negative Interference

scholarly journals Transforming Growth Factor β/Smad3 Signaling Regulates IRF-7 Function and Transcriptional Activation of the Beta Interferon Promoter

2004 ◽  
Vol 24 (3) ◽  
pp. 1411-1425 ◽  
Author(s):  
Jing Qing ◽  
Cheng Liu ◽  
Lisa Choy ◽  
Rui-Yun Wu ◽  
Joseph S. Pagano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transcriptional Activation ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Dominant Negative ◽  
Negative Interference ◽  
Rapid Induction ◽  
Dominant Negative Interference ◽  
Smad3 Expression

ABSTRACT The rapid induction of alpha interferon (IFN-α) and IFN-β expression plays a critical role in the innate immune response against viral infection. We studied the effects of transforming growth factor β (TGF-β) and its intracellular effectors, the Smads, on the function of IRF-7, an essential transcription factor for IFN-α and -β induction. IRF-7 interacted with Smads, and IRF-7, but not IRF-3, cooperated with Smad3 to activate IFN-β transcription. This transcriptional cooperation occurred at the IRF-binding sequences in the IFN-β promoter, and dominant-negative interference with TGF-β receptor signaling and Smad3 function decreased IRF-7-mediated transcription. Furthermore, elimination of Smad3 expression in Smad3−/− fibroblasts delayed and decreased double-stranded RNA-induced expression of endogenous IFN-β, whereas restoration of Smad3 expression enhanced IFN-β induction. The IRF-7-Smad3 cooperativity resulted from the regulation of the transactivation activity of IRF-7 by Smad3, and dominant-negative interference with Smad3 function decreased IRF-7 activity. Consistent with the regulation by Smad3, the transcriptional activity of IRF-7 depended on and was regulated by TGF-β signaling. Our studies underscore a role of TGF-β/Smad3 signaling in IRF-7-mediated induction of IFN-β expression.

Gli proteins encode context-dependent positive and negative functions: implications for development and disease

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3205-3216 ◽  
Author(s):  
A. Ruiz i Altaba
Keyword(s):  
Nuclear Localization ◽  
Protein Function ◽  
Hedgehog Signaling ◽  
Functional Divergence ◽  
Dominant Negative ◽  
Full Length ◽  
Gli Proteins ◽  
A Cell ◽  
Context Dependent ◽  
Modified Forms

Several lines of evidence implicate zinc finger proteins of the Gli family in the final steps of Hedgehog signaling in normal development and disease. C-terminally truncated mutant GLI3 proteins are also associated with human syndromes, but it is not clear whether these C-terminally truncated Gli proteins fulfil the same function as full-length ones. Here, structure-function analyses of Gli proteins have been performed using floor plate and neuronal induction assays in frog embryos, as well as induction of alkaline phosphatase (AP) in SHH-responsive mouse C3H10T1/2 (10T1/2) cells. These assays show that C-terminal sequences are required for positive inducing activity and cytoplasmic localization, whereas N-terminal sequences determine dominant negative function and nuclear localization. Analyses of nuclear targeted Gli1 and Gli2 proteins suggest that both activator and dominant negative proteins are modified forms. In embryos and COS cells, tagged Gli cDNAs yield C-terminally deleted forms similar to that of Ci. These results thus provide a molecular basis for the human Polydactyly type A and Pallister-Hall Syndrome phenotypes, derived from the deregulated production of C-terminally truncated GLI3 proteins. Analyses of full-length Gli function in 10T1/2 cells suggest that nuclear localization of activating forms is a regulated event and show that only Gli1 mimics SHH in inducing AP activity. Moreover, full-length Gli3 and all C-terminally truncated forms act antagonistically whereas Gli2 is inactive in this assay. In 10T1/2 cells, protein kinase A (PKA), a known inhibitor of Hh signaling, promotes Gli3 repressor formation and inhibits Gli1 function. Together, these findings suggest a context-dependent functional divergence of Gli protein function, in which a cell represses Gli3 and activates Gli1/2 prevents the formation of repressor Gli forms to respond to Shh. Interpretation of Hh signals by Gli proteins therefore appears to involve a fine balance of divergent functions within each and among different Gli proteins, the misregulation of which has profound biological consequences.

scholarly journals Roles of Autocrine TGF-β Receptor and Smad Signaling in Adipocyte Differentiation

2000 ◽  
Vol 149 (3) ◽  
pp. 667-682 ◽  
Author(s):  
Lisa Choy ◽  
Jeremy Skillington ◽  
Rik Derynck
Keyword(s):  
Adipocyte Differentiation ◽  
Inhibitory Effect ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Induced Responses ◽  
Type Ii ◽  
Negative Regulators ◽  
Dominant Negative Interference ◽  
Β Receptor

TGF-β inhibits adipocyte differentiation, yet is expressed by adipocytes. The function of TGF-β in adipogenesis, and its mechanism of action, is unknown. To address the role of TGF-β signaling in adipocyte differentiation, we characterized the expression of the TGF-β receptors, and the Smads which transmit or inhibit TGF-β signals, during adipogenesis in 3T3-F442A cells. We found that the cell-surface availability of TGF-β receptors strongly decreased as adipogenesis proceeds. Whereas mRNA levels for Smads 2, 3, and 4 were unchanged during differentiation, mRNA levels for Smads 6 and 7, which are known to inhibit TGF-β responses, decreased severely. Dominant negative interference with TGF-β receptor signaling, by stably expressing a truncated type II TGF-β receptor, enhanced differentiation and decreased growth. Stable overexpression of Smad2 or Smad3 inhibited differentiation and dominant negative inhibition of Smad3 function, but not Smad2 function, enhanced adipogenesis. Increased Smad6 and Smad7 levels blocked differentiation and enhanced TGF-β–induced responses. The inhibitory effect of Smad7 on adipocyte differentiation and its cooperation with TGF-β was associated with the C-domain of Smad7. Our results indicate that endogenous TGF-β signaling regulates the rate of adipogenesis, and that Smad2 and Smad3 have distinct functions in this endogenous control of differentiation. Smad6 and Smad7 act as negative regulators of adipogenesis and, even though known to inhibit TGF-β responses, enhance the effects of TGF-β on these cells.

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