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10.1128/MCB.22.20.7004-7014.2002 http://scihub22266oqcxt.onion/10.1128/MCB.22.20.7004-7014.2002 12242281!139825!12242281     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Cell+Biol 2002 ; 22 (20): 7004-14 Nephropedia Template TP {{tp|p=12242281|t=2002. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin |pdf=|usr=}}{{12242281}} gab.com Text Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin JO: Mol Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=12242281 #FOAvip Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor containing an inducibly expressed HIF-1alpha subunit and a constititutively expressed HIF-1beta subunit. Under hypoxic conditions, the HIF-1alpha subunit accumulates due to a decrease in the rate of proteolytic degradation, and the resulting HIF-1alpha-HIF-1beta heterodimers undergo posttranslational modifications that promote transactivation. Recent studies suggest that amplified signaling through phosphoinositide 3-kinase, and its downstream target, mTOR, enhances HIF-1-dependent gene expression in certain cell types. In the present study, we have explored further the linkage between mTOR and HIF-1 in PC-3 prostate cancer cells treated with hypoxia or the hypoxia mimetic agent, CoCl(2). Pretreatment of PC-3 cells with the mTOR inhibitor, rapamycin, inhibited both the accumulation of HIF-1alpha and HIF-1-dependent transcription induced by hypoxia or CoCl(2). Transfection of these cells with wild-type mTOR enhanced HIF-1 activation by hypoxia or CoCl(2), while expression of a rapamycin-resistant mTOR mutant rendered both HIF-1alpha stabilization and HIF-1 transactivating function refractory to inhibition by rapamycin. Studies with GAL4-HIF-1alpha fusion proteins pinpointed the oxygen-dependent degradation domain as a critical target for the rapamycin-sensitive, mTOR-dependent signaling pathway leading to HIF-1alpha stabilization by CoCl(2). These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress. Twit Text FOAVip Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin ????Mol Cell Biol http://www.kidney.de/pget.php?&tw=1&pmid=12242281 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=12242281 #FOAvip English Wikipedia <ref>{{Cite pmid|12242281}}</ref> Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin #MMPMID12242281 Hudson CC; Liu M; Chiang GG; Otterness DM; Loomis DC; Kaper F; Giaccia AJ; Abraham RT Mol Cell Biol 2002[Oct]; 22 (20): 7004-14 PMID12242281show ga Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor containing an inducibly expressed HIF-1alpha subunit and a constititutively expressed HIF-1beta subunit. Under hypoxic conditions, the HIF-1alpha subunit accumulates due to a decrease in the rate of proteolytic degradation, and the resulting HIF-1alpha-HIF-1beta heterodimers undergo posttranslational modifications that promote transactivation. Recent studies suggest that amplified signaling through phosphoinositide 3-kinase, and its downstream target, mTOR, enhances HIF-1-dependent gene expression in certain cell types. In the present study, we have explored further the linkage between mTOR and HIF-1 in PC-3 prostate cancer cells treated with hypoxia or the hypoxia mimetic agent, CoCl(2). Pretreatment of PC-3 cells with the mTOR inhibitor, rapamycin, inhibited both the accumulation of HIF-1alpha and HIF-1-dependent transcription induced by hypoxia or CoCl(2). Transfection of these cells with wild-type mTOR enhanced HIF-1 activation by hypoxia or CoCl(2), while expression of a rapamycin-resistant mTOR mutant rendered both HIF-1alpha stabilization and HIF-1 transactivating function refractory to inhibition by rapamycin. Studies with GAL4-HIF-1alpha fusion proteins pinpointed the oxygen-dependent degradation domain as a critical target for the rapamycin-sensitive, mTOR-dependent signaling pathway leading to HIF-1alpha stabilization by CoCl(2). These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress. |*Helix-Loop-Helix Motifs[MESH] |*Transcriptional Activation[MESH] |Cell Hypoxia[MESH] |Chromones/pharmacology[MESH] |Cobalt/pharmacology[MESH] |DNA-Binding Proteins/genetics/*metabolism/physiology[MESH] |Enzyme Inhibitors/pharmacology[MESH] |Glucose Transporter Type 1[MESH] |Humans[MESH] |Hypoxia-Inducible Factor 1[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit[MESH] |Leupeptins/pharmacology[MESH] |Monosaccharide Transport Proteins/genetics[MESH] |Morpholines/pharmacology[MESH] |Nuclear Proteins/genetics/*metabolism/physiology[MESH] |Phosphoinositide-3 Kinase Inhibitors[MESH] |Protein Kinase Inhibitors[MESH] |Protein Kinases/genetics/*metabolism[MESH] |Recombinant Fusion Proteins/genetics/metabolism/physiology[MESH] |Sirolimus/pharmacology[MESH] |TOR Serine-Threonine Kinases[MESH] |Transcription Factors/genetics/*metabolism/physiology[MESH] |Transcription, Genetic/drug effects[MESH]Regulation of hypoxia-inducible factor 1alpha expression and function (epmc).pdf DeepDyve Pubget Overpricing