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| Status |
Public on Aug 01, 2008 |
| Title |
C-terminal diversity within the p53 family accounts for differences in DNA binding and transcriptional activity |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The p53 family is known as a family of transcription factors with functions in tumor suppression and development. Whereas the central DNA binding domain is highly conserved among the three family members p53, p63 and p73, the C-terminal domains (CTDs) are diverse and subject to alternative splicing and post-translational modification. Here we demonstrate that the CTDs strongly influence DNA binding and transcriptional activity. While p53 and the p73 isoform p73gamma have basic CTDs and form weak sequence-specific protein-DNA complexes, the major p73 isoforms alpha, beta and delta have neutral CTDs and bind DNA strongly. A basic CTD has been previously shown to enable sliding along the DNA backbone and to facilitate the search for binding sites in the complex genome. Our experiments, however, reveal that a basic CTD also reduces protein-DNA complex stability, intranuclear mobility, promoter occupancy in vivo, transgene activation and induction of cell cycle arrest or apoptosis. A basic CTD in p53 and p73gamma therefore provides both positive and negative regulatory functions presumably to enable rapid switching of protein activity in response to stress. In contrast, most p73 isoforms exhibit constitutive DNA binding activity consistent with a predominant role in developmental control.
Keywords: Adenoviros, p73 / p53
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| Overall design |
Infection of H1299 cell with different p73/p53 constructs by adenoviral system
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| Contributor(s) |
Sauer M, Bretz AC, Beinoraviciute-Kellner R, Beitzinger M, Burek CJ, Rosenwald A, Harms GS, Stiewe T |
| Citation(s) |
18267967 |
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| Submission date |
Aug 02, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Christof Burek |
| E-mail(s) |
christof.burek@mail.uni-wuerzburg.de
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| Phone |
++49 (0)931 20147696
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| Organization name |
Universitaet Wuerzburg
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| Department |
Pathologie
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| Lab |
Rosenwald
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| Street address |
Josef-schneider-Str. 2
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| City |
Wuerzburg |
| ZIP/Postal code |
97080 |
| Country |
Germany |
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| Platforms (2) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (11)
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| GSM124854 |
p53 family members in myogenic differentiation mock 0 h |
| GSM124864 |
p53 family members in myogenic differentiation DeltaNp73 0 h |
| GSM124865 |
p53 family members in myogenic differentiation DeltaNp73 6h |
| GSM124866 |
p53 family members in myogenic differentiation mock 24 h |
| GSM124867 |
p53 family members in myogenic differentiation DeltaNp72 24h |
| GSM124868 |
p53 family members in myogenic differentiation mock 6 h |
| GSM214758 |
H1299 cell infected with an GFP construct |
| GSM214759 |
H1299 cell infected with an p53 construct |
| GSM214760 |
H1299 Cell line infected with an truncated p53 adenovirus |
| GSM214761 |
H1299 cell line infected with p73 containing adenoviral construct |
| GSM214762 |
H1299 Cell line infected with an truncated p73 adenovirus |
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| Relations |
| BioProject |
PRJNA101861 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8660_RAW.tar |
10.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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