Aggresome-like structure induced by isothiocyanates is novel proteasome-dependent degradation machinery.
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.
Mi
Lixin
L
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA. lm293@georgetown.edu
Gan
Nanqin
N
Chung
Fung-Lung
FL
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015415:Biomarkers; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D017510:Protein Folding; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D014404:Tubulin; C058305:phenethyl isothiocyanate; C031403:benzyl isothiocyanate; D046988:Proteasome Endopeptidase Complex; C016766:sulforaphane
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