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 a...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展开更多
Proteasome-mediated degradation and autophagy are the two major pathways mediating the turnover of cellularproteins.The proteasomal pathway is known to be a highly specific and regulated process mediating the degradat...Proteasome-mediated degradation and autophagy are the two major pathways mediating the turnover of cellularproteins.The proteasomal pathway is known to be a highly specific and regulated process mediating the degradationof short-lived proteins such as many important factors involved in cellular signaling.In contrast,it is generally thoughtthat autophagy is rather nonselective as it is responsible for the bulk degradation of long-lived proteins and organelles.Challenging this general view,in this issue of Cell Research,Qing et al.report that selective degradation of the IκBkinase(IKK)triggered by the loss of Hsp90 function is mediated by autophagy[1].展开更多
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
文摘Proteasome-mediated degradation and autophagy are the two major pathways mediating the turnover of cellularproteins.The proteasomal pathway is known to be a highly specific and regulated process mediating the degradationof short-lived proteins such as many important factors involved in cellular signaling.In contrast,it is generally thoughtthat autophagy is rather nonselective as it is responsible for the bulk degradation of long-lived proteins and organelles.Challenging this general view,in this issue of Cell Research,Qing et al.report that selective degradation of the IκBkinase(IKK)triggered by the loss of Hsp90 function is mediated by autophagy[1].
