PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11485818

MDM2: life without p53.

S Daujat·H Neel·J Piette
View original source ↗Export metadata ↓

Abstract

The MDM2 protein suppresses the ability of p53 to inhibit cellular proliferation or to induce cell death. This property underlies the oncogenic potential of MDM2, which is overexpressed in various human tumours. However, MDM2 also has p53-independent activities, which we focus on here. Similar to other oncogenes, surveillance pathways might counteract the deleterious effects of deregulated MDM2 expression. These pathways need to be inactivated for MDM2 oncogenic activity, which targets p53 but also other proteins.

Explore related subjects

3T3 CellsAnimalsCell Cycle ProteinsCell DeathCell DivisionDNA-Binding ProteinsE2F Transcription FactorsGenes, Tumor SuppressorHumansMiceModels, BiologicalModels, GeneticNuclear ProteinsProtein BindingProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Transcription FactorsTumor Protein p73Tumor Suppressor Protein p53Tumor Suppressor ProteinsJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Daujat, H Neel, J Piette. 2001. MDM2: life without p53.. https://doi.org/10.1016/s0168-9525(01)02369-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2019

Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance.

Obesity is an increasing pathophysiological problem in developed societies. Despite all major progress in understanding molecular mechanisms of obesity, currently available anti-obesity drugs have shown limited efficacy with severe side effects. CRISPR interference (CRISPRi) mechanism based on catalytically dead Cas9 (dCas9) and single guide RNA (sgRNA) was combined with a targeted nonviral gene delivery system to treat obesity and obesity-induced type 2 diabetes. A fusion peptide targeting a vascular and cellular marker of adipose tissue, prohibitin, was developed by conjugation of adipocyte targeting sequence (CKGGRAKDC) to 9-mer arginine (ATS-9R). (dCas9/sgFabp4) + ATS-9R oligoplexes showed effective condensation and selective delivery into mature adipocytes. Targeted delivery of the CRISPRi system against Fabp4 to white adipocytes by ATS-9R induced effective silencing of Fabp4, resulting in reduction of body weight and inflammation and restoration of hepatic steatosis in obese mice. This RNA-guided DNA recognition platform provides a simple and safe approach to regress and treat obesity and obesity-induced metabolic syndromes.

3T3 Cells↗
PubMed2007

Shape-engineered fibroblasts: cell elasticity and actin cytoskeletal features characterized by fluorescence and atomic force microscopy.

The regulation of cell shape, which determines cell behaviors including adhesion, spreading, migration, and proliferation in an engineered artificial extracellular milieu, is an important task in tissue engineering and in development of functional biomaterials. To deepen the understandings of shape-dependent cell mechanics, the cell elasticity and structural features of the actin cytoskeleton (CSK) were characterized for shape-engineered fibroblasts; round and spindle-shaped cells cultured on photolithographically microprocessed surfaces, employing the cellular microindentation tests and fluorescence observation of actin CSK by the combination of atomic force microscopy (AFM) and fluorescence microscopy (FM). The relationships among cell elasticity, the structural features of actin CSK, and engineered cell shape were analyzed and compared with those of control cells that had been cultured on nonprocessed surfaces (termed naturally extended cells). Results showed that the spindle-shaped cells with sparse or no apical stress fibers (ASFs) exhibited similar stiffness to that of the naturally extended cells with dense ASFs. The elasticity of spindle-shaped cells was affected only slightly by the stress fiber (SF) density, which is in marked contrast to the significant correlation shown between cell elasticity and SF density in naturally extended cells. This result implies that the elasticity of regionally restricted adhesion-surface-induced shape-engineered cells, particularly of highly elongated cells, is affected predominantly by cell shape rather than by structural features of SFs.

3T3 Cells↗
PubMed2007

Regulation of PAI-1 gene expression during adipogenesis.

Obesity is characterized by elevated levels of circulating plasminogen activator inhibitor-1 (PAI-1), which contribute towards the development of secondary disorders such as type 2 diabetes mellitus and cardiovascular complications. This increase in plasma PAI-1 levels is attributed to an increase in PAI-1 derived from adipose tissue. This study shows that adipose tissue evolved into a major PAI-1 producing organ by gaining capacity during adipocyte differentiation to respond to inducers of PAI-1 transcription. This is mediated by a decrease in E2F1 protein levels, an increase in pRB levels and a decrease in pRB phosphorylation, all leading to a decrease in levels of free E2F, a known transcriptional repressor of PAI-1. Depletion of E2F1-3 was sufficient for inducers such as insulin to potently induce PAI-1 gene expression in pre-adipocytes. Conversely, forced release of pRB-bound endogenous E2F using cell-penetrating peptides can suppress PAI-1 gene expression in adipocytes. This study describes the novel paradigm of cellular differentiation-associated increase in PAI-1 gene expression which is mediated by a decrease in repressor activity, and describes a way of desensitising terminally differentiated cells to PAI-1 inducing agents by restoring endogenous repressor activity.

3T3 Cells↗