| Life or death: p53-induced apoptosis requires DNA binding cooperativity. | |
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MedLine Citation:
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PMID: 20948308 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The tumor suppressor p53 provides exquisite protection from cancer by balancing cell survival and death in response to stress. Sustained stress or irreparable damage trigger p53's killer functions to permanently eliminate genetically-altered cells as a potential source of cancer. To prevent the unnecessary loss of cells that could cause premature aging as a result of stem cell attrition, the killer functions of p53 are tightly regulated and balanced against protector functions that promote damage repair and support survival in response to low stress or mild damage. In molecular terms these p53-based cell fate decisions involve protein interactions with cofactors and modifying enzymes, which modulate the activation of distinct sets of p53 target genes. In addition, we demonstrate that part of this regulation occurs at the level of DNA binding. We show that the killer function of p53 requires the four DNA binding domains within the p53 tetramer to interact with one another. These intermolecular interactions enable cooperative binding of p53 to less perfect response elements in the genome, which are present in many target genes essential for apoptosis. Modulating p53 interactions within the tetramer could therefore present a novel promising strategy to fine-tune p53-based cell fate decisions. |
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Authors:
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Katharina Schlereth; Joël P Charles; Anne C Bretz; Thorsten Stiewe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-11 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 9 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-28 Completed Date: 2011-03-07 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 4068-76 Citation Subset: IM |
Affiliation:
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Molecular Oncology, Philipps-University Marburg, Marburg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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physiology* Base Sequence Binding Sites Consensus Sequence DNA / genetics, metabolism* Gene Expression Regulation Humans Molecular Sequence Data Protein Binding Protein Processing, Post-Translational Tumor Suppressor Protein p53 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Tumor Suppressor Protein p53; 9007-49-2/DNA |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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