Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathway of growth inhibitory cellular signal transduction by transforming growth factor beta 1 is largely unknown. Although several cellular proteins have been shown to be involved in the pathway, others remain to be identified. To search for other involved proteins, differentially expressed genes were examined in two human hepatoma cell lines that were respectively sensitive and resistant to growth inhibition by TGF-beta 1. Two such genes (SB31 and SB16) were characterized and found to be 100% homologous to leucine-rich alpha 2-glycoprotein and the ribosomal protein S25, respectively. SB31 was coordinately expressed with the TGF-beta I type II receptor, implicating a possible interaction. Expression of both genes in different cell lines can be broadly correlated with the sensitivity of the cell lines to growth inhibition by TGF-beta 1. SB16 expression is strongly suppressed in rat liver regeneration after partial hepatectomy, suggesting that it may have a role in liver growth.
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PMID:Differentially expressed genes in TGF-beta 1 sensitive and resistant human hepatoma cells. 788 5

An amino acid starvation-induced mRNA, increased up to 4-fold in the absence of amino acids, was identified previously as rat 60 S subunit ribosomal protein L17. The data presented here demonstrate that among ribosomal proteins, L17, as well as the smaller subunit ribosomal protein S25, are uniquely regulated by amino acid deprivation of cells; the increase in L17 and S25 mRNA content in response to substrate starvation is not shared by the 11 other ribosomal proteins tested. When rat Fao hepatoma cells were incubated in the presence of actinomycin D, the L17 mRNA level decayed below the basal level, regardless of medium amino acid content, and nuclear run-off assays confirmed that nutrient starvation leads to enhanced transcription of the L17 ribosomal protein gene. Likewise, the induction of S25 mRNA also was prevented in the presence of actinomycin D. Furthermore, the induction of L17 and S25 mRNA content was blocked by cycloheximide, demonstrating the requirement for a newly synthesized protein in the signaling pathway. Northern analysis with RNA isolated from cytoplasmic, polysomal, and nuclear enriched fractions indicated that the starvation-dependent increase in the S25 and L17 mRNAs is retained within the nucleus and not is available for translation. Amino acid refeeding of the cells caused the translocation of the stored nuclear mRNAs to the polysomal fraction.
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PMID:Nuclear retention of the induced mRNA following amino acid-dependent transcriptional regulation of mammalian ribosomal proteins L17 and S25. 814 59

Coordinate regulation of the ribosomal protein genes is entrusted to a number of signal transduction pathways that can abruptly induce or silence the ribosomal genes. We have uncovered a cellular model system, which selectively induces the ribosomal protein S25 gene in hepatoma cells that are stressed by nutrient deprivation. Our results indicate that p53 along with two other identified proteins, MTF-1 and La, post-transcriptionally regulate the synthesis of the S25 protein by controlling the nuclear export of the stress-induced S25 mRNA. This system is unique in that the nuclear-retained S25 mRNA is exported to the cytosol only upon replenishment or alternatively after prolonged starvation to participate in a p53-mediated apoptotic sequence of events. This p53-dependent survival or death pathway involves a previously unreported protein relationship among these three actors, one of which, MTF-1, has not yet been shown to have RNA-binding characteristics.
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PMID:Ribosomal protein S25 mRNA partners with MTF-1 and La to provide a p53-mediated mechanism for survival or death. 1174 12