Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of various inflammatory mechanisms and oxidative stress in the development of atherosclerosis and arterial hypertension (AH) has been increasingly acknowledged during recent years. Hypertension per se or factors that cause hypertension along with other complications lead to infiltration of activated leukocytes in the vascular wall, where these cells contribute to the development of vascular injury by releasing cytokines, oxygen radicals, and other toxic mediators. However, molecular mechanisms underlying leukocyte activation at transcriptional level in AH are still far from being clear. To solve this problem we employed cDNA microarray technology to reveal the differences in gene expression in peripheral blood leukocytes from patients with AH compared with healthy individuals. The microarray data were verified by a semi-quantitative RT-PCR method. We found 25 genes with differential expression in leukocytes from AH patients among which 21 genes were upregulated and 4 genes were downregulated. These genes are implicated in apoptosis (CASP2, CASP4, and CASP8, p53, UBID4, NAT1, and Fte-1), inflammatory response (CAGC, CXCR4, and CX3CR1), control of MAP kinase function (PYST1, PAC1, RAF1, and RAFB1), vesicular trafficking of molecules among cellular organelles (GDI-1 and GDI-2), cell redox homeostasis (GLRX), cellular stress (HSPA8 and HSP40), and other processes. Gene expression pattern of the majority of genes was similar in AH patients independent of the disease stage and used hypotensive therapy, but was clearly different from that of normotensive subjects.
 ...
PMID:Altered gene expression pattern in peripheral blood leukocytes from patients with arterial hypertension. 1734 25

Requiem, a hypothesized transcription factor with apoptosis-related activity, was previously shown to be a potential cell engineering gene target for improving recombinant protein production. Requiem suppression has resulted in improved viable cell density and extended culture viability, leading to an overall improvement in recombinant protein productivity. However, not much is known about the function of requiem. We found that requiem is highly conserved at both nucleotide and amino acid levels in Chinese hamster ovary (CHO) cells when compared to human and mouse sequences, suggesting that requiem's functional role is evolutionary well conserved. Upon inducing requiem over-expression, proliferation rates of CHO cells were significantly decreased with doubling times increased by 26%. Interestingly, the over-expression of requiem did not decrease cell viability and could not induce apoptosis. However, requiem sensitized the cells to increased caspase-9 activities under staurosporine-induced apoptosis, suggesting that it has a role to play in mitochondria-mediated apoptosis under staurosporine treatment. The nuclear localization of REQUIEM in CHO cells and its conserved plant homeodomain (PHD) zinc fingers seem to further support the hypothesis that requiem encodes for a potential transcription factor. Upon requiem over-expression, we found that the differentially expressed genes involved in transcriptional regulation and cell proliferation and growth were associated both upstream and downstream of p53.
 ...
PMID:Elucidating the role of requiem in the growth and death of Chinese hamster ovary cells. 2001 65

The d4 family of transcription factors consists of three members in mammals. DPF1/neuro-d4 is expressed mainly in neurons and the peripheral nervous system, and is important for brain development. DPF2/requiem/ubi-d4 is expressed ubiquitously and presumably functions as an apoptotic factor, especially during the deprivation of trophic factors. DPF3/cer-d4 is expressed in neurons and in the heart, and is important for heart development and function in zebrafish. In Drosophila, there is only one member, dd4, whose function is still unknown, but it is expressed in many tissues and is particularly abundant in the brain of developing embryos and in adults. Here, we present DPFF-1, the only member of this family of proteins in the nematode C. elegans. DPFF-1 is similar to its mammalian homolog DPF2/requiem/ubi-d4 because it is ubiquitously expressed during embryogenesis and in adult tissues, and because it is important for the induction of germ cell apoptosis during stress. Here, we show that dpff-1 null mutant animals produce less progeny than wild-type nematodes, presumably due to meiotic defects. Gonads of dpff-1 deficient animals showed more germ cells in pachytene and overexpressed the P-MPK-1 signal. Additionally, these animals presented higher levels of p53-induced germ cell apoptosis than wild-type animals. Furthermore, we observed that dpff-1 deficient animals are more sensitive to heat shock. This is the first report showing that the d4 family of transcription factors could be involved in meiosis and stress protection.
 ...
PMID:DPFF-1 transcription factor deficiency causes the aberrant activation of MPK-1 and meiotic defects in the Caenorhabditis elegans germline. 2894 Jun 92