Searching across hundreds of databases
The transcriptional activator p53 is a tumor suppressor protein that controls cellular pathways important for cell fate decisions, including cell cycle arrest, senescence, and apoptosis. It functions as a tetramer by binding to specific DNA sequences known as response elements (REs) to control transcription via interactions with co-regulatory complexes. Despite its biological importance, the mechanism by which p53 binds REs remains unclear. To address this, we have used an in vitro single molecule fluorescence approach to quantify the dynamic binding of full-length human p53 to five native REs in real time under equilibrium conditions. Our approach enabled us to quantify the oligomeric state of DNA-bound p53. We found little evidence that dimer/DNA complexes form as intermediates en route to binding or dissociation of p53 tetramer/DNA complexes. Interestingly, however, at some REs dimers can rapidly exchange from tetramer/DNA complexes. Real time kinetic measurements enabled us to determine rate constants for association and dissociation at all five REs, which revealed two kinetically distinct populations of tetrameric p53/RE complexes. For the less stable population, the rate constants for dissociation were larger at REs closest to consensus, showing that the more favorable binding sequences form the least kinetically stable complexes. Together our single molecule measurements provide new insight into mechanisms by which tetrameric p53 forms complexes on different native REs.
Pubmed ID: 37582100 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A sequence analysis tool providing a simple but detailed analysis of human genes and their variations. For each gene, a gene-gene relationship network can be generated based on protein-protein interaction data, metabolic pathway connections and extended through phylogenetic relations. Snap provides tools for designing sequence primers and evaluating RNA splicing effects of single SNPs - known from the databases or defined by you. Primers can be designed for the amplification or sequencing of cDNA, genomic DNA, introns only or exons only.
View all literature mentionsSolvers, or optimizers, are software tools that help users find the best way to allocate scarce resources. The resources may be raw materials, machine time or people time, money, or anything else in limited supply. The best or optimal solution may mean maximizing profits, minimizing costs, or achieving the best possible quality. An almost infinite variety of problems can be tackled this way, but here are some typical examples: Finance and Investment Working capital management involves allocating cash to different purposes (accounts receivable, inventory, etc.) across multiple time periods, to maximize interest earnings. Capital budgeting involves allocating funds to projects that initially consume cash but later generate cash, to maximize a firm''s return on capital. Portfolio optimization -- creating efficient portfolios -- involves allocating funds to stocks or bonds to maximize return for a given level of risk, or to minimize risk for a target rate of return. Manufacturing Job shop scheduling involves allocating time for work orders on different types of production equipment, to minimize delivery time or maximize equipment utilization. Blending (of petroleum products, ores, animal feed, etc.) involves allocating and combining raw materials of different types and grades, to meet demand while minimizing costs. Cutting stock (for lumber, paper, etc.) involves allocating space on large sheets or timbers to be cut into smaller pieces, to meet demand while minimizing waste. Distribution and Networks Routing (of goods, natural gas, electricity, digital data, etc.) involves allocating something to different paths through which it can move to various destinations, to minimize costs or maximize throughput. Loading (of trucks, rail cars, etc.) involves allocating space in vehicles to items of different sizes so as to minimize wasted or unused space. Scheduling of everything from workers to vehicles and meeting rooms involves allocating capacity to various tasks in order to meet demand while minimizing overall costs.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
