p53 domains: identification and characterization of two autonomous DNA-binding regions.

@article{Wang1993p53DI,
  title={p53 domains: identification and characterization of two autonomous DNA-binding regions.},
  author={Y. Wang and M. Reed and P. Wang and J. E. Stenger and G. Mayr and M. Anderson and J. Schwedes and P. Tegtmeyer},
  journal={Genes \& development},
  year={1993},
  volume={7 12B},
  pages={
          2575-86
        }
}
We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p53. We find that p53 has two autonomous DNA-binding regions. One domain, from amino acid 280 to 390, forms stable tetramers and binds DNA nonspecifically. The biological significance, if any, of this DNA-binding activity is not known. A second domain, from amino acid 80 to 290, does not form stable tetramers under stringent conditions but binds DNA both specifically and… Expand

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It is proposed that DNA structure-selective binding of mutp53 proteins is the basis for the well-documented interaction ofmutp53 with MAR elements and for transcriptional activities mediates by mutp 53. Expand
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Purified p53 produced from baculovirus-infected insect cells binds preferentially to supercoiled DNA, forming bands with lower electrophoretic mobility, consistent with a model in which p53 binds to right-handed or left-handed strand crossings. Expand
Crystal Structure of the Mouse p53 Core DNA-binding Domain at 2.7 Å Resolution*
TLDR
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TLDR
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References

SHOWING 1-10 OF 59 REFERENCES
A DNA binding domain is contained in the C-terminus of wild type p53 protein.
TLDR
A comparison of the binding activities of the various purified p53 proteins, assessed by their ability to bind DNA cellulose columns, indicated that wild type p53 has a higher affinity to DNA than have mutant p53 forms. Expand
Regulation of the specific DNA binding function of p53
TLDR
It is shown that p53 DNA binding is cryptic but can be activated by cellular factors acting on a C-terminal regulatory domain of p53, which may be critical in regulation of its ability to arrest cell growth and thus its tumor suppressor function. Expand
Activation of the cryptic DNA binding function of mutant forms of p53.
TLDR
Together, these data show that some mutant forms of p53 harbour the wild-type machinery required to engage in sequence-specific DNA binding and define a signalling pathway whose inactivation may directly result in a loss in p53 function. Expand
Tight DNA binding and oligomerization are dispensable for the ability of p53 to transactivate target genes and suppress transformation.
TLDR
Findings indicate that dimerization‐defective p53 is biologically active and may engage in productive sequence‐specific DNA interactions in vivo, and probably leads to cooperative binding to specific DNA sequences. Expand
Analysis of a protein-binding domain of p53.
TLDR
T-antigen binding was unaffected by tumor-derived mutations which have been associated with the wild-type conformation of p53 but was greatly reduced by mutations which were previously shown to alter p53 conformation. Expand
Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53.
TLDR
It is demonstrated, by filter binding and gel mobility-shift assays, that wild-type p53 binds with similar affinities to MCK and RGC sites but less tightly to the SV40 site. Expand
A transcriptionally active DNA-binding site for human p53 protein complexes.
TLDR
A reiterative selection procedure is used to identify new specific binding sites for p53, using nuclear extracts from normal human fibroblasts as the source of p53 protein, and the preferred consensus is the palindrome GGACATGCCCGGGCATGTCC. Expand
Identification of p53 as a sequence-specific DNA-binding protein
TLDR
Data suggest that a function of p53 may be mediated by its ability to bind to specific DNA sequences in the human genome, and that this activity is altered by mutations that occur in human tumors. Expand
Direct interaction between the transcriptional activation domain of human p53 and the TATA box-binding protein.
TLDR
Protein affinity chromatography is used to show that the cellular transcription factor, p53, interacts directly and specifically with yeast TBP, which supports a general model in which DNA-bound activator proteins activate transcription by interacting with TBP. Expand
Wild-type p53 activates transcription in vitro
TLDR
It is shown that intact purified wild-type human and murine p53 proteins strongly activate transcription in vitro, and this activation depends on the ability of p53 to bind to a template bearing a p53-binding sequence. Expand
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