Geldanamycin selectively targets the nascent form of ERBB3 for degradation

摘要: Heat shock protein 90 (HSP90) targets a broad spectrum of client proteins with divergent modes interaction and consequences. The homologous epidermal growth factor receptor (EGFR) ERBB2 receptors as well kinase-deficient mutants thereof differ in their requirement for HSP90 the nascent versus mature state receptor. Specific features kinase domain have been implicated selective association ERBB2. We evaluated role ERBB3 is naturally deficient, central mediator cell survival stress response primary dimerization partner signaling. Cellular studies indicate that, similar to EGFR, geldanamycin (GA) sensitivity binding resides dependent on presence ERBB3. Furthermore, despite its intrinsic lack activity contrast reported GA appears be exclusive. Geldanamycin disrupts inhibits maturation at an early stage synthesis, prior export from ER. Studies photo-convertible fusion suggest later maturation, possibly through putative structural proofreading.