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The assembly of p53 or GR heterocomplexes with hsp90 and immunophilins was not affected by PFTО± either in vivo or in vitro and did not affect the nuclear translocation of either transcription factor. PFTО± did, however, cause a left shift in the dexamethasone dose response curve by increasing intracellular dexamethasone concentration, apparently by competing for dexamethasone efflux from the cell. At concentrations where PFTО± blocks p53-mediated induction of p21/Waf-1 in human embryonic kidney cells, we observed no inhibition of GR-mediated induction of a chloramphenicol acetyl transferase reporter in LMCAT cells. Because it is important for the mechanistic study of this machinery to identify unique inhibitors of chaperone action, we have examined the effect of PFTО± on transcriptional activation, the hsp90 heterocomplex assembly, and hsp90-dependent nuclear translocation for both p53 and the GR. However, the laboratory that discovered pifithrin recently reported that the compound also inhibits heat shock and glucocorticoid receptor (GR) signaling, and they suggested that PFTО± targets a factor common to all three signal transduction pathways, such as the hsp90/hsp70-based chaperone machinery (Komarova, E. This flexible data is inclined to analyse as soon as you wish.Pifithrin-О± (PFTО±) was originally thought to be a specific inhibitor of signaling by the tumor suppressor protein p53.

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