Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumor suppressor gene, which is considered the guardian of the genome, encodes a phosphoprotein, which is a sequence-specific transcriptional activator or repressor of target genes. The role of p53 in developmental processes has not been studied extensively, although its expression appears to undergo temporal and spatial changes during prenatal and postnatal development. In the present study, we assessed the levels of p53 mRNA and protein in the developing rat brain and its relation to developmental cell death. Furthermore, we investigated the potential role of n-methyl-d-aspartate (NMDA) receptors in regulating p53 expression, since these receptors are involved in the control of cell death. We found that p53 mRNA and protein were detectable in the rat brain throughout perinatal development. In embryos, p53 immunoreactivity was mainly localized in the nuclei of neuroepithelial cells, with a maximum in staining at embryonic day (E)12. In the neuroepithelium, we also found significant numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells, both in dividing periventricular cells and in migrating neurons. In neonates, immediately after birth there was a reduction in the number of apoptotic cells, which then increased to reach a maximum at postnatal day (P)5. Postnatally, apoptotic as well as p53-positive cells were detected in most brain areas. P53 immunoreactivity was also highest on P5. In most cells, p53 immunoreactivity and the TUNEL signal colocalized. P53 immunoreactivity as well as the number of TUNEL- positive cells were dramatically decreased in the brains of newborns treated with MK-801, an NMDA receptor antagonist. Our results show that p53 is involved in the control of developmental cell death, and that NMDA receptors play a regulatory role in the expression of the p53 gene, and thus in apoptosis occurring in the developing rat brain.
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PMID:p53 expression and regulation by NMDA receptors in the developing rat brain. 1034 Jul 50

GD3 ganglioside induces apoptosis in several cell types, but the molecular events through which this occurs are largely unknown. We investigated the apoptotic effects of GD3 expression using U-1242 MG glioblastoma cells, as these cells synthesize almost exclusively GM3 and GM2 but not GD3. To express GD3 under the control of the TetOn system with minimum leakage, we modified the system by constructing a single tri-cistronic retrovirus vector containing three genes separated by two internal ribosome entry sites: (a) transcriptional silencer, tTS; (b) mutant of reverse transcriptional activator, rtTA2(S)-M2 (provided by H. Bujard, Heidelberg, Germany); and (c) enhanced green fluorescent protein (EGFP), as an indicator of the tri-cistronic gene expression. Using flow cytometry, we selected glioma cells (U1242MG-GD3 clone) that express high levels of GD3 in response to doxycycline. Expression of GD3 was associated with apoptosis as verified by annexin-V binding, TdT-mediated dUTPnick end-labelling assay (TUNEL), and EGFP degradation. GD3-induced apoptosis occurred via caspase-8 activation, as GD3 caused cleavage of caspase-8 and inhibition of caspase-8 activation by zlETD-fmk minimized GD3-induced apoptosis.
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PMID:Endogenous GD3 ganglioside induces apoptosis in U-1242 MG glioma cells. 1644 17