Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Putting p53 in Context.

ABSTRACT: TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?

SUBMITTER: Kastenhuber ER

PROVIDER: S-EPMC5743327 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Putting p53 in Context.

Kastenhuber Edward R ER Lowe Scott W SW

Cell 20170901 6

TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfun ...[more]

PMID: 28886379

Similar Datasets

Putting visual object recognition in context.

Project description:Context plays an important role in visual recognition. Recent studies have shown that visual recognition networks can be fooled by placing objects in inconsistent contexts (e.g. a cow in the ocean). To understand and model the role of contextual information in visual recognition, we systematically and quantitatively investigated ten critical properties of where, when, and how context modulates recognition including amount of context, context and object resolution, geometrical structure of context, context congruence, time required to incorporate contextual information, and temporal dynamics of contextual modulation. The tasks involve recognizing a target object surrounded with context in a natural image. As an essential benchmark, we first describe a series of psychophysics experiments, where we alter one aspect of context at a time, and quantify human recognition accuracy. To computationally assess performance on the same tasks, we propose a biologically inspired context aware object recognition model consisting of a two-stream architecture. The model processes visual information at the fovea and periphery in parallel, dynamically incorporates both object and contextual information, and sequentially reasons about the class label for the target object. Across a wide range of behavioral tasks, the model approximates human level performance without retraining for each task, captures the dependence of context enhancement on image properties, and provides initial steps towards integrating scene and object information for visual recognition.

| S-EPMC8459751 | biostudies-literature

Putting the treatment of paediatric schistosomiasis into context.

Project description:Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6-15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel.The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600 mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet.This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children.

| S-EPMC5384153 | biostudies-literature

Putting pleiotropy and selection into context defines a new paradigm for interpreting genetic data.

Project description:Natural selection shapes many human genes, including some related to complex diseases. Understanding how selection affects genes, especially pleiotropic ones, may be important in evaluating disease associations and the role played by environmental variation. This may be of particular interest for genes with antagonistic roles that cause divergent patterns of selection. The lectin-like low-density lipoprotein 1 receptor, encoded by OLR1, is exemplary. It has antagonistic functions in the cardiovascular and immune systems because the same protein domain binds oxidized low-density lipoprotein and bacterial cell wall proteins, the former contributing to atherosclerosis and the latter presumably protecting from infection. We studied patterns of selection in this gene, in humans and nonhuman primates, to determine whether variable selection can lead to conflicting results in cardiovascular disease association studies.We analyzed sequences from 11 nonhuman primate species, as well as single-nucleotide polymorphisms and sequence data from multiple human populations. Results indicate that the derived allele is favored across primate lineages (probably because of recent positive selection). However, both the derived and ancestral alleles were maintained in human populations, especially European ones (possibly because of balancing selection derived from dual roles of LOX-1). Balancing selection likely reflects response to diverse environmental pressures among humans.These data indicate that differential selection patterns, within and between species, in OLR1 render association studies difficult to replicate even if the gene is etiologically connected to cardiovascular disease. Selection analyses can identify genes exhibiting gene-environment interactions critical for unraveling disease association.

| S-EPMC3889706 | biostudies-literature

Putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions.

Project description:A complete understanding of complex dynamic cellular processes such as cell migration or cell adhesion requires the integration of atomic level structural information into the larger cellular context. While direct atomic-level information at the cellular level remains inaccessible, electron microscopy, electron tomography and their associated computational image processing approaches have now matured to a point where sub-cellular structures can be imaged in three dimensions at the nanometer scale. Atomic-resolution information obtained by other means can be combined with this data to obtain three-dimensional models of large macromolecular assemblies in their cellular context. This article summarizes some recent advances in this field.

| S-EPMC3294126 | biostudies-literature

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes.

Project description:The tumor suppressor gene TP53 is the most frequently mutated gene in numerous cancer types, including prostate cancer (PCa). Specifically, missense mutations in TP53 are selectively enriched in PCa, and cluster to particular "hot spots" in the p53 DNA binding domain with mutation at the R273 residue occurring most frequently. While this residue is similarly mutated to R273C-p53 or R273H-p53 in all cancer types examined, in PCa selective enrichment of R273C-p53 is observed. Importantly, examination of clinical datasets indicated that TP53 heterozygosity can either be maintained or loss of heterozygosity (LOH) occurs. Thus, to mimic tumor-associated mutant p53, R273C-p53 and R273H-p53 isogenic PCa models were developed in the presence or absence of wild-type p53. In the absence of wild-type p53, both R273C-p53 and R273H-p53 exhibited similar loss of DNA binding, transcriptional profiles, and loss of canonical tumor suppressor functions associated with wild-type p53. In the presence of wild-type p53 expression, both R273C-p53 and R273H-p53 supported canonical p53 target gene expression yet elicited distinct cistromic and transcriptional profiles when compared to each other. Moreover, heterozygous modeling of R273C-p53 or R273H-p53 expression resulted in distinct phenotypic outcomes in vitro and in vivo. Thus, mutant p53 acts in a context-dependent manner to elicit pro-tumorigenic transcriptional profiles, providing critical insight into mutant p53-mediated prostate cancer progression.

| S-EPMC8755525 | biostudies-literature

Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala.

Project description:A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats.

| S-EPMC5597864 | biostudies-literature

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-23 | GSE157337 | GEO

Context is everything: extrinsic signalling and gain-of-function p53 mutants.

Project description:The TP53 genomic locus is a target of mutational events in at least half of cancers. Despite several decades of study, a full consensus on the relevance of the acquisition of p53 gain-of-function missense mutants has not been reached. Depending on cancer type, type of mutations and other unidentified factors, the relevance for tumour development and progression of the oncogenic signalling directed by p53 mutants might significantly vary, leading to inconsistent observations that have fuelled a long and fierce debate in the field. Here, we discuss how interaction with the microenvironment and stressors might dictate the gain-of-function effects exerted by individual mutants. We report evidence from the most recent literature in support of the context dependency of p53 mutant biology. This perspective article aims to raise a discussion in the field on the relevance that context might have on p53 gain-of-function mutants, assessing whether this should generally be considered a cell non-autonomous process.

| S-EPMC7090043 | biostudies-literature

Mutant p53 elicits context-dependent pro-tumorigenic phenotypes (microarray)

Project description:These studies characterized R273C-p53 and R273H-p53 in prostate cancer cells

2021-12-23 | GSE157336 | GEO

Putting cumulative (dis)advantages in context: Comparing the role of educational inequality in later-life functional health trajectories in England and Germany.

Project description:BackgroundThe cumulative (dis)advantage (CAD) perspective more and more is examined in a comparative way, to highlight the role of context in generating inequality over the life course. This study adds to this field of research by examining trajectories of activities of daily living (ADL) in later life by educational level in a country comparison of England and Germany, emphasizing differing institutional conditions.MethodData used are the English Longitudinal Study of Ageing (ELSA; 11,352 individuals) and the German subsample of the Survey of Health and Retirement in Europe (SHARE; 5,573 individuals). Using population averaged Poisson panel regression models, 12-year trajectories of six birth cohorts are investigated, covering the age range of 50 to 90 years.ResultsRespondents in England have a higher level of limitations at age 50, and more limited increases over age than in Germany. An educational gradient exists in both countries at age 50. Notably, the educational gradient increases for more recently born cohorts, but declines with increasing age in England, while in Germany educational differences increase for more recently born cohort only.DiscussionThe current study indicates that CAD processes between educational groups are context sensitive. While England showed convergence of disparities with increasing age, in Germany no differential development was found.

| S-EPMC7773250 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data