Hsp90 Regulates p50 cdc37 Function during the Biogenesis of the Active Conformation of the Heme-regulated eIF2α Kinase

摘要: Recent studies indicate that p50 cdc37 facilitates Hsp90-mediated biogenesis of certain protein kinases. In this report, we examined whether is required for the heme-regulated eIF2α kinase (HRI) in reticulocyte lysate. interacted with nascent HRI co-translationally and interaction persisted during maturation activation HRI. stimulated HRI's response to heme deficiency, but did not activate per se. function was specific immature inactive forms kinase. Analysis mutant Cdc37 gene products indicated N-terminal portion HRI, Hsp90, while C-terminal Hsp90. The Hsp90-specific inhibitor geldanamycin disrupted ability both Hsp90 bind promote its activation, disrupt native association A truncated inhibited prevented bound irrespective treatment. Additionally, complexes were detected cultured K562 erythroleukemia cells. These results suggest provides an activity essential via a process regulated by nucleotide-mediated conformational switching partner