Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

c-Ski inhibits transforming growth factor-beta (TGF-beta) signaling through interaction with Smad proteins. c-Ski represses Smad-mediated transcriptional activation, probably through its action as a transcriptional co-repressor. c-Ski also inhibits TGF-beta-induced downregulation of genes such as c-myc. However, mechanisms for transcriptional regulation of target genes by c-Ski have not been fully determined. In this study, we examined how c-Ski inhibits both TGF-beta-induced transcriptional activation and repression. DNA-affinity precipitation analysis revealed that c-Ski enhances the binding of Smad2 and 4, and to a lesser extent Smad3, to both CAGA and TGF-beta1 inhibitory element probes. A c-Ski mutant, which is unable to interact with Smad4, failed to enhance the binding of Smad complex on these probes and to inhibit the Smad-responsive promoter. These results suggest that stabilization of inactive Smad complexes on DNA is a critical event in c-Ski-mediated inhibition of TGF-beta signaling.
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PMID:c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. 1510 21

This study used cDNA microarray technology to compare gene expression profiles in acute myeloblastic leukaemia (AML) with cDNA dot-blot and real time PCR analysis of cDNA transcripts to confirm array data. Patient AML marrow samples and AML cell lines were compared with normal/non-AML samples. Screening revealed five particular genes to be significantly differentially expressed across the sample groups. The migration-inhibitory factor-related-proteins 8 and 14 (MRP-8 and MRP-14) genes, the products of which inhibit cell migration and differentiation were the most highly expressed in non-malignant cells. The high-mobility-group-protein gene (HMG-1) was up regulated in leukaemic samples and cell lines, which may be associated with aggressive disease. Also upregulated in malignant samples were genes encoding c-myc and glutathione-S-transferase pi (GSTP), the latter implicated in chemotherapy resistance. Faulty expression of such genes may contribute to the pathogenesis of AML and resistance to treatment.
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PMID:DNA microarray screening of differential gene expression in bone marrow samples from AML, non-AML patients and AML cell lines. 1515 96

Doxorubicin is a DNA-damaging drug, commonly used for treatment of cancer patients. Doxorubicin causes not only cytotoxic and cytostatic effects, but also inhibits metastasis formation, while TGFbeta1 (Transforming Growth Factor-beta1) is a cytokine that is often up-regulated in human cancers and can promote metastasis formation. We have studied the influence of Doxorubicin on TGFbeta signaling in tumor cells. Here we have demonstrated that Doxorubicin inhibited TGFbeta-signaling in human lung adenocarcinoma A549 cells, namely, it blocked TGFbeta1-induced activation of Smad3-responsive CAGA(12)-Luc reporter, but did not affect c-myc-Luc reporter. That effect was observed as early as after 1-3 h of treating these cells with Doxorubicin, while the other drugs cisplatin or methotrexate did not alter activation of CAGA(12)-Luc reporter under the same conditions. Besides, after 1 h action, Doxorubicin abrogated TGFbeta-induced translocation of Smad3-protein from the cytoplasm to the nucleus. Down-regulation of expression of Smad2, Smad3, and Smad4 proteins, and up-regulation of inhibitory Smad7 protein upon Doxorubicin treatment, were found after 12-24 h of Doxorubicin treatment. Phosphorylation of Smad2/3 proteins was also affected by Doxorubicin. Summarizing, we have found that human tumor cells treatment with Doxorubicin resulted in the inhibition of TGFbeta-signaling at both early (1 h) and later (12 h) stages of the drug action. Such inhibition can be a new potential mechanism for Doxorubicin action towards tumor cells.
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PMID:Doxorubicin inhibits TGF-beta signaling in human lung carcinoma A549 cells. 1860 4