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Aggresome-like structure induced by isothiocyanates is novel proteasome-dependent degradation machinery.

ABSTRACT: Unwanted or misfolded proteins are either refolded by chaperones or degraded by the ubiquitin-proteasome system (UPS). When UPS is impaired, misfolded proteins form aggregates, which are transported along microtubules by motor protein dynein towards the juxta-nuclear microtubule-organizing center to form aggresome, a single cellular garbage disposal complex. Because aggresome formation results from proteasome failure, aggresome components are degraded through the autophagy/lysosome pathway. Here we report that small molecule isothiocyanates (ITCs) can induce formation of aggresome-like structure (ALS) through covalent modification of cytoplasmic alpha- and beta-tubulin. The formation of ALS is related to neither proteasome inhibition nor oxidative stress. ITC-induced ALS is a proteasome-dependent assembly for emergent removal of misfolded proteins, suggesting that the cell may have a previously unknown strategy to cope with misfolded proteins.

SUBMITTER: Mi L

PROVIDER: S-EPMC2748326 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Aggresome-like structure induced by isothiocyanates is novel proteasome-dependent degradation machinery.

Mi Lixin L Gan Nanqin N Chung Fung-Lung FL

Biochemical and biophysical research communications 20090812 2

Unwanted or misfolded proteins are either refolded by chaperones or degraded by the ubiquitin-proteasome system (UPS). When UPS is impaired, misfolded proteins form aggregates, which are transported along microtubules by motor protein dynein towards the juxta-nuclear microtubule-organizing center to form aggresome, a single cellular garbage disposal complex. Because aggresome formation results from proteasome failure, aggresome components are degraded through the autophagy/lysosome pathway. Here ...[more]

PMID: 19682429

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