NF-кB promotes aggresome formation via upregulating HDAC6 and in turn maintaining Vimentin cage

The study reveals a new mechanism guiding MG132-triggered aggresome formation. NF-кB is quickly activated upon exposure to MG132, and NF-кB upregulates the misfolded protein recognizing factor HDCA6. In addition to collecting misfolded proteins, HDAC6 also binds Vimentin and maintains the Vimentin cage, which quarantines toxic misfolded proteins and protects cells from being toxified by those protein toxicants. Therapeutically, chemical inactivation of NF-кB synergizes MG132-induced cytotoxicity, providing a new strategy to defeat cancers.