Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

STIM1 (where STIM is stromal interaction molecule) is a candidate tumour suppressor gene that maps to human chromosome 11p15.5, a region implicated in a variety of cancers, particularly embryonal rhabdomyosarcoma. STIM1 codes for a transmembrane phosphoprotein whose structure is unrelated to that of any other known proteins. The precise pathway by which STIM1 regulates cell growth is not known. In the present study we screened gene databases for STIM1-related sequences, and have identified and characterized cDNA sequences representing a single gene in humans and other vertebrates, which we have called STIM2. We identified a single STIM homologue in Drosophila melanogaster (D-Stim) and Caenorhabditis elegans, but no homologues in yeast. STIM1, STIM2 and D-Stim have a conserved genomic organization, indicating that the vertebrate family of two STIM genes most probably arose from a single ancestral gene. The three STIM proteins each contain a single SAM (sterile alpha-motif) domain and an unpaired EF hand within the highly conserved extracellular region, and have coiled-coil domains that are conserved in structure and position within the cytoplasmic region. However, the STIM proteins diverge significantly within the C-terminal half of the cytoplasmic domain. Differential levels of phosphorylation appear to account for two molecular mass isoforms (105 and 115 kDa) of STIM2. We demonstrate by mutation analysis and protein sequencing that human STIM2 initiates translation exclusively from a non-AUG start site in vivo. STIM2 is expressed ubiquitously in cell lines, and co-precipitates with STIM1 from cell lysates. This association into oligomers in vivo indicates a possible functional interaction between STIM1 and STIM2. The structural similarities between STIM1, STIM2 and D-STIM suggest conserved biological functions.
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PMID:Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins. 1146 38

The p53 tumour suppressor gene is a transcription factor that can induce cell cycle arrest and apoptosis. In response to various stress-inducing signals, p53 level increases and this is accompanied with increased activities of p53. Interestingly, the methylxanthine caffeine can abrogate the p53 accumulation induced by certain DNA-damaging agents by an unknown mechanism. In an effort to understand how different signals induce p53, human tumour cell lines were treated with combinations of various stress-inducing agents and caffeine. Caffeine inhibited the accumulation of p53 induced by leptomycin B (LMB), an inhibitor of CRM1, but not N-acetyl-leu-leu-norleucinal, a proteasome inhibitor. Furthermore, caffeine also inhibited the accumulation of p53 by a variety of stress-inducing agents in vivo, such as 5-fluorouracil, doxorubicin, mitomycin C, camptothecin and roscovitine. However, caffeine failed to affect the accumulation of p53 in hypoxia (HYP)-treated cells. These results suggested that HYP must use a distinct pathway from most DNA-damaging and stress-inducing agents to induce p53.
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PMID:Hypoxia induces p53 through a pathway distinct from most DNA-damaging and stress-inducing agents. 1280 44

The p53 tumour suppressor is stabilised following exposure to genotoxic agents, such as gamma-radiation. Cell responses to p53 stabilisation include induction of apoptosis and/or cell cycle arrest. Several studies have suggested that gamma-radiation stabilises p53 by blocking ubiquitin mediated proteolysis. Here we have compared the biological activities of p53 stabilized following exposure to gamma-radiation or treatment with the proteosome inhibitor N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) in MCF7 cells with wild type p53. Stabilisation of p53 by ALLN was reversible and was not blocked by caffeine. Although ALLN was a more effective p53 stabilising agent than gamma-radiation, ALLN was not as effective at inducing cell cycle arrest/apoptosis as gamma-radiation. Although p53 stabilised by ALLN and gamma-radiation were both able to bind DNA and activate transcription, ALLN did not increase expression of BAX, which is involved in p53-induced apoptosis. Therefore, p53 stabilised by different agents is not always biologically active to the same extent and additional alterations triggered by gamma-radiation may enable p53 to activate a subset of critical target genes, such as BAX, which are required for p53 responses.
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PMID:The biological response of MCF7 breast cancer cells to proteosome inhibition or gamma-radiation is unrelated to the level of p53 induction. 1463 87

The E6 protein of human papillomavirus type 16 is essential for the oncogenic transformation process induced by these viruses. Here we expressed the E6 protein in Saccharomyces cerevisiae (which lacks p53) in order to determine if E6 interacts with normal cell functioning, independently of the p53 tumour suppressor factor. We observed a higher resistance to caffeine, hydrogen peroxide and to pheromone, but not to high temperature, starvation and osmostress. Measurement of the relative expression levels of target genes of the signalling pathways, involved in the latter stressful stimuli, led us to conclude that such pathways are differently regulated in the presence of E6.
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PMID:Expression of HPV16 E6 oncoprotein increases resistance to several stress conditions in Saccharomyces cerevisiae. 1585 Nov 6