Site-Specific Recognition by an Isolated DNA-Binding Domain of the Sine Oculis Protein†

Biochemistry ◽  
1997 ◽  
Vol 36 (12) ◽  
pp. 3680-3686 ◽  
Author(s):  
Tony R. Hazbun ◽  
Florence L. Stahura ◽  
Michael C. Mossing
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Site Specific ◽  
Sine Oculis ◽  
Specific Recognition

DNA-binding regulates site-specific ubiquitination of IRF-1

2013 ◽  
Vol 449 (3) ◽  
pp. 707-717 ◽  
Author(s):  
Vivien Landré ◽  
Emmanuelle Pion ◽  
Vikram Narayan ◽  
Dimitris P. Xirodimas ◽  
Kathryn L. Ball
Keyword(s):  
Dna Binding ◽  
E3 Ligase ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Docking Site ◽  
Interacting Protein ◽  
Site Specific ◽  
E3 Ligases ◽  
Intrinsically Disordered ◽  
C Terminus

Understanding the determinants for site-specific ubiquitination by E3 ligase components of the ubiquitin machinery is proving to be a challenge. In the present study we investigate the role of an E3 ligase docking site (Mf2 domain) in an intrinsically disordered domain of IRF-1 [IFN (interferon) regulatory factor-1], a short-lived IFNγ-regulated transcription factor, in ubiquitination of the protein. Ubiquitin modification of full-length IRF-1 by E3 ligases such as CHIP [C-terminus of the Hsc (heat-shock cognate) 70-interacting protein] and MDM2 (murine double minute 2), which dock to the Mf2 domain, was specific for lysine residues found predominantly in loop structures that extend from the DNA-binding domain, whereas no modification was detected in the more conformationally flexible C-terminal half of the protein. The E3 docking site was not available when IRF-1 was in its DNA-bound conformation and cognate DNA-binding sequences strongly suppressed ubiquitination, highlighting a strict relationship between ligase binding and site-specific modification at residues in the DNA-binding domain. Hyperubiquitination of a non-DNA-binding mutant supports a mechanism where an active DNA-bound pool of IRF-1 is protected from polyubiquitination and degradation.

scholarly journals Activation of CREB/ATF Sites by Polyomavirus Large T Antigen

2005 ◽  
Vol 79 (7) ◽  
pp. 4180-4190 ◽  
Author(s):  
Tara M. Love ◽  
Rowena de Jesus ◽  
Jennifer A. Kean ◽  
Qing Sheng ◽  
Andrew Leger ◽  
...  
Keyword(s):  
Dna Binding ◽  
T Antigen ◽  
Binding Domain ◽  
Cell Phenotype ◽  
Dna Binding Domain ◽  
Large T Antigen ◽  
Direct Role ◽  
Site Specific ◽  
Creb Phosphorylation

ABSTRACT Polyomavirus large T antigen (LT) has a direct role in viral replication and a profound effect on cell phenotype. It promotes cell cycle progression, immortalizes primary cells, blocks differentiation, and causes apoptosis. While much of large T function is related to its effects on tumor suppressors of the retinoblastoma susceptibility (Rb) gene family, we have previously shown that activation of the cyclin A promoter can occur through a non-Rb-dependent mechanism. Here we show that activation occurs via an ATF/CREB site. Investigation of the mechanism indicates that large T can synergize with CREB family members to activate transcription. Experiments with Gal4-CREB constructs show that synergy is independent of CREB phosphorylation by protein kinase A. Examination of synergy with Gal4-CREB deletion constructs indicates that large T acts on the constitutive activation domain of CREB. Large T can bind to CREB in vivo. Genetic analysis shows that the DNA-binding domain (residues 264 to 420) is sufficient to activate transcription when it is localized to the nucleus. Further analysis of the DNA-binding domain shows that while site-specific DNA binding is not required, non-site-specific DNA binding is important for the activation. Thus, CREB binding and DNA binding are both important for large T activation of CREB/ATF sites. In contrast to previous models where large T transactivation occurred indirectly, these results also suggest that large T can act directly at promoters to activate transcription.

scholarly journals Role of cysteine residues in regulation of p53 function.

1995 ◽  
Vol 15 (7) ◽  
pp. 3892-3903 ◽  
Author(s):  
R Rainwater ◽  
D Parks ◽  
M E Anderson ◽  
P Tegtmeyer ◽  
K Mann
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Redox Regulation ◽  
Binding Domain ◽  
Zinc Binding ◽  
Cysteine Residues ◽  
Dna Binding Domain ◽  
Site Specific ◽  
Functional Consequences

Previous studies of p53 have implicated cysteine residues in site-specific DNA binding via zinc coordination and redox regulation (P. Hainaut and J. Milner, Cancer Res. 53:4469-4473, 1993; T. R. Hupp, D. W. Meek, C. A. Midgley, and D. P. Lane, Nucleic Acids Res. 21:3167-3174, 1993). We show here that zinc binding and redox regulation are, at least in part, distinct determinants of the binding of p53 to DNA. Moreover, by substituting serine for each cysteine in murine p53, we have investigated the roles of individual cysteines in the regulation of p53 function. Substitution of serine for cysteine at position 40, 179, 274, 293, or 308 had little or no effect on p53 function. In contrast, replacement of cysteine at position 173, 235, or 239 markedly reduced in vitro DNA binding, completely blocked transcriptional activation, and led to a striking enhancement rather than a suppression of transformation by p53. These three cysteines have been implicated in zinc binding by X-ray diffraction studies (Y. Cho, S. Gorina, P.D. Jeffrey, and N.P. Pavletich, Science 265:346-355, 1994); our studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to studies demonstrate the functional consequences of the inability of the central DNA-binding domain of p53 to bind zinc. Lastly, substitutions for cysteines at position 121, 132, 138, or 272 partially blocked both transactivation and the suppression of transformation by p53. These four cysteines are located in the loop-sheet-helix region of the site-specific DNA-binding domain of p53. Like the cysteines in the zinc-binding region, therefore, these cysteines may cooperate to modulate the structure of the DNA-binding domain. Our findings argue that p53 is subject to more than one level of conformational modulation through oxidation-reduction of cysteines at or near the p53-DNA interface.

Two of the Five Zinc Fingers in the Zap1 Transcription Factor DNA Binding Domain Dominate Site-Specific DNA Binding†

Biochemistry ◽  
2003 ◽  
Vol 42 (4) ◽  
pp. 1053-1061 ◽  
Author(s):  
M. V. Evans-Galea ◽  
E. Blankman ◽  
D. G. Myszka ◽  
A. J. Bird ◽  
D. J. Eide ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Zinc Fingers ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Site Specific

scholarly journals Characterization of the DNA-binding domain of the mouse uterine estrogen receptor using site-specific polyclonal antibodies

1993 ◽  
Vol 268 (14) ◽  
pp. 10296-10302
Author(s):  
M. Ikeda ◽  
F. Ogata ◽  
S.W. Curtis ◽  
D.B. Lubahn ◽  
F.S. French ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Dna Binding ◽  
Polyclonal Antibodies ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Site Specific

scholarly journals The p53 C Terminus Controls Site-Specific DNA Binding and Promotes Structural Changes within the Central DNA Binding Domain

2015 ◽  
Vol 57 (6) ◽  
pp. 1034-1046 ◽  
Author(s):  
Oleg Laptenko ◽  
Idit Shiff ◽  
Will Freed-Pastor ◽  
Andrew Zupnick ◽  
Melissa Mattia ◽  
...  
Keyword(s):  
Dna Binding ◽  
Structural Changes ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Site Specific ◽  
C Terminus

NMR studies of the R2 repeat and related peptide fragments of the DNA binding domain of c-Myb. New light on the structure and folding of R2.

1999 ◽  
Vol 96 (9/10) ◽  
pp. 1580-1584 ◽  
Author(s):  
I. Ségalas ◽  
S. Desjardins ◽  
H. Oulyadi ◽  
Y. Prigent ◽  
S. Tribouillard ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Peptide Fragments ◽  
Nmr Studies ◽  
Related Peptide
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