| 1 | Hsp90 inhibition results in autophagy-mediated proteasome-independent degradation of IκB kinase(IKK)显示文摘Autophagic and proteasomal proteolysis are two major pathways for degradation of cellular constituents.Currentmodels suggest that autophagy is responsible for the nonselective bulk degradation of long-lived proteins and organelleswhile the proteasome specifically degrades short-lived proteins including misfolded proteins caused by the absence ofHsp90 function.Here,we show that the IκB kinase(IKK),an essential activator of NF-κB,is selectively degraded byautophagy when Hsp90 is inhibited by geldanamycin(GA),a specific Hsp90 inhibitor showing highly effective anti-tumoractivity.We find that in this case inactivation of ubiquitination or proteasome fails to block IKK degradation.However,inhibition of autophagy by an autophagy inhibitor or knockout of Atg5,a key component of the autophagy pathway,significantly rescues IKK from GA-induced degradation.These findings provide the first evidence that an Hsp90 clientmay be degraded by a mechanism different from the proteasome pathway and establish a molecular link among Hsp90,NF-κB and | Guoliang Qing Pengrong Yan Gutian Xiao | 2006 | Cell Research2006，16，11： | 7 |
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