ArticleMolecular and cellular biology1999
An ATP/ADP-dependent molecular switch regulates the stability of p53-DNA complexes.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Regulators mount up: the metabolic roles of apoptotic proteins.Frontiers in cell death · 2023Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Effect ofFrontiers in cell and developmental biology · 2022Article
- Regulation of Cellular Metabolism and Hypoxia by p53.Cold Spring Harbor perspectives in medicine · 2016Review
- Cancer stem cell theory and the warburg effect, two sides of the same coin?International journal of molecular sciences · 2014Article
- TIGAR, TIGAR, burning bright.Cancer & metabolism · 2014Article
- Uncovering the basis of ATP hydrolysis activity in purified human p53 protein: a reinvestigation.PloS one · 2014Article
- Mitochondrial dysfunction impairs tumor suppressor p53 expression/function.The Journal of biological chemistry · 2011Article
- The biology of lysine acetylation integrates transcriptional programming and metabolism.Nutrition & metabolism · 2011Article
- p53 and metabolism.Nature reviews. Cancer · 2009Review
- Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense.Seminars in cancer biology · 2009Review
- Versatile functions of p53 protein in multicellular organisms.Biochemistry. Biokhimiia · 2007Review
- The structure of p53 tumour suppressor protein reveals the basis for its functional plasticity.The EMBO journal · 2006Article
- NAD+ modulates p53 DNA binding specificity and function.Molecular and cellular biology · 2004Article
- p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB.The EMBO journal · 2003Article
- Several regions of p53 are involved in repression of RNA polymerase III transcription.Oncogene · 2002Article
- Article
- The interaction of p53 with the nuclear matrix is mediated by F-actin and modulated by DNA damage.Oncogene · 2002Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interaction with DNA is essential for the tumor suppressor functions of p53. We now show, for the first time, that the interaction of p53 with DNA can be stabilized by small molecules, such as ADP and dADP. Our results also indicate an ATP/ADP molecular switch mechanism which determines the off-on states for p53-DNA binding. This ATP/ADP molecular switch requires dimer-dimer interaction of the p53 tetramer. Dissociation of p53-DNA complexes by ATP is independent of ATP hydrolysis. Low-level ATPase activity is nonetheless associated with ATP-p53 interaction and may serve to regenerate ADP-p53, thus recycling the high-affinity DNA binding form of p53. The ATP/ADP regulatory mechanism applies to two distinct types of p53 interaction with DNA, namely, sequence-specific DNA binding (via the core domain of the p53 protein) and binding to sites of DNA damage (via the C-terminal domain). Further studies indicate that ADP not only stabilizes p53-DNA complexes but also renders the complexes susceptible to dissociation by specific p53 binding proteins. We propose a model in which the DNA binding functions of p53 are regulated by an ATP/ADP molecular switch, and we suggest that this mechanism may function during the cellular response to DNA damage.
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