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p53 oligomerization and DNA looping are linked with transcriptional activation.

1994; Springer Nature; Volume: 13; Issue: 24 Linguagem: Inglês

10.1002/j.1460-2075.1994.tb06947.x

1460-2075

Judith E. Stenger, P Tegtmeyer, Gregory A. Mayr, Michael Reed, Yuan Wang, Pengliang Wang, P.V.C. Hough, Iris A. Mastrangelo,

Animal Genetics and Reproduction

Research Article15 December 1994free access p53 oligomerization and DNA looping are linked with transcriptional activation. J.E. Stenger J.E. Stenger Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P. Tegtmeyer P. Tegtmeyer Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author G.A. Mayr G.A. Mayr Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author M. Reed M. Reed Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author Y. Wang Y. Wang Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P. Wang P. Wang Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P.V. Hough P.V. Hough Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author I.A. Mastrangelo I.A. Mastrangelo Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author J.E. Stenger J.E. Stenger Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P. Tegtmeyer P. Tegtmeyer Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author G.A. Mayr G.A. Mayr Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author M. Reed M. Reed Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author Y. Wang Y. Wang Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P. Wang P. Wang Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author P.V. Hough P.V. Hough Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author I.A. Mastrangelo I.A. Mastrangelo Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. Search for more papers by this author Author Information J.E. Stenger1, P. Tegtmeyer1, G.A. Mayr1, M. Reed1, Y. Wang1, P. Wang1, P.V. Hough1 and I.A. Mastrangelo1 1Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794. The EMBO Journal (1994)13:6011-6020https://doi.org/10.1002/j.1460-2075.1994.tb06947.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info We examined the role of p53 oligomerization in DNA binding and in transactivation. By conventional electron microscopy (EM) and scanning transmission EM, we find that wild-type tetramers contact 18-20 bp at single or tandem 19 bp consensus sequences and also stack in apparent register, tetramer on top of tetramer. Stacked tetramers link separated DNA binding sites with DNA loops. Interestingly, the p53(1-320) segment, which lacks the C-terminal tetramerization domain, binds DNA consensus sites as stacked oligomers. Although the truncated protein binds DNA with reduced efficiency, it nevertheless induces DNA looping by self-association. p53, therefore, has a C-terminal tetramerization domain that enhances DNA binding and a non-tetrameric oligomerization domain that stacks p53 at consensus sites and loops separated consensus sites via protein-protein interactions. Using model promoters, we demonstrate that wild-type and tetramerization-deficient p53s activate transcription well when tandem consensus sites are proximal to TATA sequences and poorly when tandem sites are distal. In the presence of proximal sites, however, stimulation by distal sites increases 25-fold. Tetramerization and stacking of tetramers, therefore, provide dual mechanisms to augment the number of p53 molecules available for activation through p53 response elements. DNA looping between separated response elements further increases the concentration of local p53 by translocating distally bound protein to the promoter. Previous ArticleNext Article Volume 13Issue 241 December 1994In this issue RelatedDetailsLoading ...