scholarly journals Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions

2004 ◽  
Vol 24 (2) ◽  
pp. 809-822 ◽  
Author(s):  
Shanru Li ◽  
Joel Weidenfeld ◽  
Edward E. Morrisey
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Binding Activity ◽  
Transcriptional Repressors ◽  
Transcription Analysis ◽  
Dna Binding Activity ◽  
The Family ◽  
Two Hybrid ◽  
Repression Domain

ABSTRACT Foxp1, Foxp2, and Foxp4 are large multidomain transcriptional regulators belonging to the family of winged-helix DNA binding proteins known as the Fox family. Foxp1 and Foxp2 have been shown to act as transcriptional repressors, while regulatory activity of the recently identified Foxp4 has not been determined. Given the importance of this Fox gene subfamily in neural and lung development, we sought to elucidate the mechanisms by which Foxp1, Foxp2, and Foxp4 repress gene transcription. We show that like Foxp1 and Foxp2, Foxp4 represses transcription. Analysis of the N-terminal repression domain in Foxp1, Foxp2, and Foxp4 shows that this region contains two separate and distinct repression subdomains that are highly homologous termed subdomain 1 and subdomain 2. However, subdomain 2 is not functional in Foxp4. Screening for proteins that interact with subdomains 1 and 2 of Foxp2 using yeast two-hybrid analysis revealed that subdomain 2 binds to C-terminal binding protein 1, which can synergistically repress transcription with Foxp1 and Foxp2, but not Foxp4. Subdomain 1 contains a highly conserved leucine zipper similar to that found in N-myc and confers homo- and heterodimerization to the Foxp1/2/4 family members. These interactions are dependent on the conserved leucine zipper motif. Finally, we show that the integrity of this subdomain is essential for DNA binding, making Foxp1, Foxp2, and Foxp4 the first Fox proteins that require dimerization for DNA binding. These data reveal a complex regulatory mechanism underlying Foxp1, Foxp2, and Foxp4 activity, demonstrating that Foxp1, Foxp2, and Foxp4 are the first Fox proteins reported whose activity is regulated by homo- and heterodimerization.

Transformation by Fos proteins requires a C-terminal transactivation domain

1993 ◽  
Vol 13 (12) ◽  
pp. 7429-7438
Author(s):  
R Wisdon ◽  
I M Verma
Keyword(s):  
Dna Binding ◽  
Leucine Zipper ◽  
Fibroblast Cell ◽  
Binding Activity ◽  
Sequence Specificity ◽  
Transactivation Domain ◽  
Functional Requirements ◽  
Dna Binding Activity ◽  
The Difference ◽  
Transforming Proteins

The Fos family of proteins now includes seven members: the retroviral proteins FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB, FosB2, Fra1, and Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not. As all family members display sequence-specific DNA-binding activity as part of a heterodimeric complex with Jun proteins, other features must account for the differences in transforming potential. We demonstrate here that all transforming members have a C-terminal transactivation domain that is lacking in nontransforming members. The nontransforming proteins Fra1 and Fra2 can be converted to transforming proteins by fusion of a transactivation domain from either FosB or VP16. We also demonstrate that differences in the basic region-leucine zipper domain affecting either the affinity or sequence specificity of DNA binding are not determinants of the difference in transforming potential among members of the Fos family. The results further define the functional requirements for transformation by Fos proteins and suggest that the subunit composition of AP1 complexes is an important determinant of mitogenic signalling capability.

Synergistic activation of transcription is mediated by the N-terminal domain of Drosophila fushi tarazu homeoprotein and can occur without DNA binding by the protein

1993 ◽  
Vol 13 (3) ◽  
pp. 1599-1609
Author(s):  
J Ananthan ◽  
R Baler ◽  
D Morrissey ◽  
J Zuo ◽  
Y Lan ◽  
...  
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Binding Activity ◽  
Protein Protein Interactions ◽  
Fushi Tarazu ◽  
Combinatorial Regulation ◽  
Dna Binding Activity ◽  
Culture Cells ◽  
Synergistic Activation ◽  
Activation Of Transcription

Synergistic activation of transcription by Drosophila segmentation genes in tissue culture cells provides a model with which to study combinatorial regulation. We examined the synergistic activation of an engrailed-derived promoter by the pair-rule proteins paired (PRD) and fushi tarazu (FTZ). Synergistic activation by PRD requires regions of the homeodomain or adjacent sequences, and that by FTZ requires the first 171 residues. Surprisingly, deletion of the FTZ homeodomain does not reduce the capacity of the protein for synergistic activation, although this mutation abolishes any detectable DNA-binding activity. This finding suggests that FTZ can function through protein-protein interactions with PRD or other components of the homeoprotein transcription complex, adding a new layer of mechanisms that could underlie the functional specificities and combinatorial regulation of homeoproteins.

scholarly journals Synergistic activation of transcription is mediated by the N-terminal domain of Drosophila fushi tarazu homeoprotein and can occur without DNA binding by the protein.

1993 ◽  
Vol 13 (3) ◽  
pp. 1599-1609 ◽  
Author(s):  
J Ananthan ◽  
R Baler ◽  
D Morrissey ◽  
J Zuo ◽  
Y Lan ◽  
...  
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Binding Activity ◽  
Protein Protein Interactions ◽  
Fushi Tarazu ◽  
Combinatorial Regulation ◽  
Dna Binding Activity ◽  
Culture Cells ◽  
Synergistic Activation ◽  
Activation Of Transcription

Synergistic activation of transcription by Drosophila segmentation genes in tissue culture cells provides a model with which to study combinatorial regulation. We examined the synergistic activation of an engrailed-derived promoter by the pair-rule proteins paired (PRD) and fushi tarazu (FTZ). Synergistic activation by PRD requires regions of the homeodomain or adjacent sequences, and that by FTZ requires the first 171 residues. Surprisingly, deletion of the FTZ homeodomain does not reduce the capacity of the protein for synergistic activation, although this mutation abolishes any detectable DNA-binding activity. This finding suggests that FTZ can function through protein-protein interactions with PRD or other components of the homeoprotein transcription complex, adding a new layer of mechanisms that could underlie the functional specificities and combinatorial regulation of homeoproteins.

scholarly journals Redox-mediated Mechanisms Regulate DNA Binding Activity of the G-group of Basic Region Leucine Zipper (bZIP) Transcription Factors inArabidopsis

2012 ◽  
Vol 287 (33) ◽  
pp. 27510-27525 ◽  
Author(s):  
Jehad Shaikhali ◽  
Louise Norén ◽  
Juan de Dios Barajas-López ◽  
Vaibhav Srivastava ◽  
Janine König ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Leucine Zipper ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Bzip Transcription Factors ◽  
Basic Region

scholarly journals Transformation by Fos proteins requires a C-terminal transactivation domain.

1993 ◽  
Vol 13 (12) ◽  
pp. 7429-7438 ◽  
Author(s):  
R Wisdon ◽  
I M Verma
Keyword(s):  
Dna Binding ◽  
Leucine Zipper ◽  
Fibroblast Cell ◽  
Binding Activity ◽  
Sequence Specificity ◽  
Transactivation Domain ◽  
Functional Requirements ◽  
Dna Binding Activity ◽  
The Difference ◽  
Transforming Proteins

The Fos family of proteins now includes seven members: the retroviral proteins FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB, FosB2, Fra1, and Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, and FosB) transform established rodent fibroblast cell lines, while three (FosB2, Fra1, and Fra2) do not. As all family members display sequence-specific DNA-binding activity as part of a heterodimeric complex with Jun proteins, other features must account for the differences in transforming potential. We demonstrate here that all transforming members have a C-terminal transactivation domain that is lacking in nontransforming members. The nontransforming proteins Fra1 and Fra2 can be converted to transforming proteins by fusion of a transactivation domain from either FosB or VP16. We also demonstrate that differences in the basic region-leucine zipper domain affecting either the affinity or sequence specificity of DNA binding are not determinants of the difference in transforming potential among members of the Fos family. The results further define the functional requirements for transformation by Fos proteins and suggest that the subunit composition of AP1 complexes is an important determinant of mitogenic signalling capability.

Global regulation of sulfur assimilation in Neurospora

1995 ◽  
Vol 73 (S1) ◽  
pp. 167-172 ◽  
Author(s):  
George A. Marzluf ◽  
Qunhui Li ◽  
Kristin Coulter
Keyword(s):  
Dna Binding ◽  
Leucine Zipper ◽  
Regulatory Protein ◽  
Binding Activity ◽  
Binding Motif ◽  
Sulfur Assimilation ◽  
Dna Binding Activity ◽  
Autogenous Control ◽  
Regulatory Circuit ◽  
Autogenous Regulation

A complex regulatory circuit controls expression of many permeases and enzymes involved in sulfur assimilation in the filamentous fungus Neurospora crassa. CYS3, the global positive-acting sulfur regulatory protein, turns on the expression of structural genes that encode sulfur enzymes when N. crassa cells are limited for sulfur. Expression of the cys-3 gene itself is highly regulated by negative-acting sulfur-controller scon genes and by autogenous regulation. The CYS3 protein is localized within the nucleus and contains a bZip DNA-binding motif and regions rich in alanine and in proline that appear to function in trans activation. Amino acid substitutions for basic or neutral amino acids in the bZip domain of CYS3 lead to significant changes in its DNA-binding activity. Key words: sulfur regulation, CYS3, autogenous control, leucine zipper, trans activation.

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