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Cited by 140

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Hsp90 inhibition results in autophagy-mediated proteasome-independent degradation of IκB kinase (IKK)

Qing, Guoliang, Yan, Pengrong, Xiao, Gutian·2006·Cell Research
DOI 10.1038/sj.cr.7310109
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Abstract

Autophagic and proteasomal proteolysis are two major pathways for degradation of cellular constituents. Current models suggest that autophagy is responsible for the nonselective bulk degradation of long-lived proteins and organelles while the proteasome specifically degrades short-lived proteins including misfolded proteins caused by the absence of Hsp90 function. Here, we show that the IkappaB kinase (IKK), an essential activator of NF-kappaB, is selectively degraded by autophagy when Hsp90 is inhibited by geldanamycin (GA), a specific Hsp90 inhibitor showing highly effective anti-tumor activity. 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 client may be degraded by a mechanism different from the proteasome pathway and establish a molecular link among Hsp90, NF-kappaB and autophagy.

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Crossref · 10.1038/sj.cr.7310109

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Citations

Cites

Research works printed but not linked: 28

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Cited by

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Metadata

Authors
Qing, G., Yan, P., & Xiao, G.
Venue
Cell Research
Publisher
Springer Science and Business Media LLC
Published
2006-11
Volume
16
Issue
11
Pages
895-901
ISSN
  • 1001-0602
  • 1748-7838
DOI
10.1038/sj.cr.7310109
Cited by
140
References
2
Language
en
Licence
www.springer.com/tdm (tdm)

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