The effect on lincRNA expression by p53 family members
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Idogawa M
PROVIDER: S-ECPF-GEOD-52739 | biostudies-other | 2014 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:To evaluate the effect on lincRNA expression by p53 family members, we overexpressed p53 family members in H1299 cells and evaluated the lincRNA expression by microarray analysis.
2014-02-05 | GSE52739 | GEO
Project description:To evaluate the effect on lincRNA expression by p53 family members, we overexpressed p53 family members in H1299 cells and evaluated the lincRNA expression by microarray analysis. lincRNA expression was measured in H1299 cells infected with adenovirus expressing LacZ, p53, p63a, p63g, p73a and p73b.
2014-02-05 | E-GEOD-52739 | biostudies-arrayexpress
Project description:To evaluate the effect on gene expression by p53 family members and AKR1B10, we overexpressed p53 family members in H1299 cells or knocked down AKR1B10 in HCT116 cells and evaluated the gene expression by microarray analysis.
2013-10-31 | GSE47096 | GEO
Project description:To evaluate the effect on gene expression by p53 family members and AKR1B10, we overexpressed p53 family members in H1299 cells or knocked down AKR1B10 in HCT116 cells and evaluated the gene expression by microarray analysis. Gene expression was measured in H1299 cells infected with adenovirus expressing p53, p63g and p73b, and in HCT116 cells transfected with siRNAs targeting AKR1B10 and then treated with adriamycin.
2013-10-31 | E-GEOD-47096 | biostudies-arrayexpress
Project description:The tumor suppressor p53 was previously shown to markedly up-regulate the expression of the PRODH gene, encoding the proline dehydrogenase (PRODH) enzyme, which catalyzes the first step in proline degradation. Also PRODH2, which degrades 4-hydroxy-L-proline, a product of protein (e.g. collagen) catabolism, was recently described as a p53 target. Here, we confirmed p53-dependent induction of endogenous PRODH in response to genotoxic damage in cell lines of different histological origin. We established that over-expression of TAp73β or TAp63β is sufficient to induce PRODH expression in p53-null cells and that PRODH expression parallels the modulation of endogenous p73 by genotoxic drugs in several cell lines. The p53, p63, and p73-dependent transcriptional activation was linked to specific intronic response elements (REs), among those predicted by bioinformatics tools and experimentally validated by a yeast-based transactivation assay. p53 occupancy measurements were validated in HCT116 and MCF7 human cell lines. Conversely, PRODH2 was not responsive to p63 nor p73 and, at best, could be considered a weak p53 target. In fact, minimal levels of PRODH2 transcript induction by genotoxic stress was observed exclusively in one of four p53 wild-type cell lines tested. Consistently, all predicted p53 REs in PRODH2 were poor matches to the p53 RE consensus and showed very weak responsiveness, only to p53, in the functional assay. Taken together, our results highlight that PRODH, but not PRODH2, expression is under the control of p53 family members, specifically p53 and p73. This supports a deeper link between proteins of the p53-family and metabolic pathways, as PRODH modulates the balance of proline and glutamate levels and those of their derivative alpha-keto-glutarate (α-KG) under normal and pathological (tumor) conditions.
| S-EPMC3704516 | biostudies-other
Project description:The p53 family members, which consist of 3 transcription factors-p53, p63, and p73-are conserved during evolution. The p53 family proteins are involved in many important cellular functions, including tumor suppression (p53 and p73), the development of epithelial cell layers (p63), and the development of central nervous system and immune system (p73). Studies on p53-like proteins in low organisms have demonstrated that their primordial functions are to maintain the genomic integrity of germ cells and ensure faithful development and reproduction. In vertebrates, the p53 family proteins retain these functions in reproduction and at the same time have developed additional important functions in reproduction, such as the regulation of embryonic implantation (p53). p53 regulates embryonic implantation through transcriptional regulation of leukemia inhibitory factor (LIF). p63, in particular TAp63, is a main regulator to protect the fidelity of female germ cells during meiotic arrest. p73, in particular TAp73, regulates the ovary function and the quality of oocytes. Loss of p53, p63, or p73 genes in female mice leads to a significant decrease in fertility. These functions of the p53 family proteins in reproduction provide a plausible explanation for positive evolutionary selection observed in a group of single nucleotide polymorphisms and haplotypes in the p53 family genes. A better understanding of the functions of the p53 family proteins in reproduction may lead to new strategies for fertility treatment.
| S-EPMC3135638 | biostudies-literature
Project description:The p53 family comprises the tumor suppressor p53 and the structural homologs p63 and p73. How the three family members cooperate in tumor suppression remains unclear. Here, we report different but complementary functions of the individual members for regulating retinoblastoma protein (RB) function during myogenic differentiation. Whereas p53 transactivates the retinoblastoma gene, p63 and p73 induce the cyclin-dependent kinase inhibitor p57 to maintain RB in an active, hypophosphorylated state. DeltaNp73 inhibits these functions of the p53 family in differentiation control, prevents myogenic differentiation, and enables cooperating oncogenes to transform myoblasts to tumorigenicity. DeltaNp73 is frequently overexpressed in rhabdomyosarcoma and essential for tumor progression in vivo. These findings establish differentiation control as a key tumor suppressor activity of the p53 family. Keywords: oligonucleotide
2006-10-16 | GSE5447 | GEO
Project description:Tumor suppressor p53 is crucial for embryonic implantation through transcriptional up-regulation of uterine leukemia inhibitory factor (LIF). This article reports that p53 and estrogen receptor ? were activated in endometrial tissues during implantation to coordinately regulate LIF production. By using human p53 knockin (Hupki) mice carrying a single nucleotide polymorphism (SNP) at codon 72 (arginine/proline), the arginine allele was demonstrated to produce higher uterine LIF levels during implantation than the proline allele. In humans, the diversity of haplotypes of the p53 gene has decreased during evolution, because the arginine allele, existing in only a subset of haplotypes, is under positive selection. This observation is consistent with previous results showing that the proline allele is enriched in patients undergoing in vitro fertilization (IVF). Studies with p63- and p73-knockout mice have demonstrated the involvement of p63 and p73 in female reproduction and their roles in egg formation and apoptosis (p63) and spindle checkpoint (p73) in female mice. Here, the role of p63 and p73 in human reproduction was investigated. Selected alleles of SNPs in p63 and p73 genes were enriched in IVF patients. These findings demonstrate that the p53 family members are involved in several steps to regulate female reproduction in mice and humans.
| S-EPMC3114525 | biostudies-literature
Project description:We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21(WAF-1/CIP1). The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21(WAF-1/CIP1). Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.
| S-EPMC321425 | biostudies-other
Project description:p53 binds to some members of the S100 family (S100B, S100A4, S100A2, and S100A1). We previously showed that both S100B and S100A4 bind to the p53 tetramerization domain, and consequently control its oligomerization state, but only S100B binds to the C-terminal negative regulatory domain (NRD). Here, we investigate other binding partners for p53 within the S100 family (S100A6 and S100A11), and show that binding to the p53 tetramerization domain seems to be a general feature of the S100 family, while binding to the NRD is a characteristic of a subset of the family.
| S-EPMC2548378 | biostudies-literature