The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress.

Published

Journal Article

The efficient clearance of cytotoxic misfolded protein aggregates is critical for cell survival. Misfolded protein aggregates are transported and removed from the cytoplasm by dynein motors via the microtubule network to a novel organelle termed the aggresome where they are processed. However, the means by which dynein motors recognize misfolded protein cargo, and the cellular factors that regulate aggresome formation, remain unknown. We have discovered that HDAC6, a microtubule-associated deacetylase, is a component of the aggresome. We demonstrate that HDAC6 has the capacity to bind both polyubiquitinated misfolded proteins and dynein motors, thereby acting to recruit misfolded protein cargo to dynein motors for transport to aggresomes. Indeed, cells deficient in HDAC6 fail to clear misfolded protein aggregates from the cytoplasm, cannot form aggresomes properly, and are hypersensitive to the accumulation of misfolded proteins. These findings identify HDAC6 as a crucial player in the cellular management of misfolded protein-induced stress.

Full Text

Duke Authors

Cited Authors

  • Kawaguchi, Y; Kovacs, JJ; McLaurin, A; Vance, JM; Ito, A; Yao, TP

Published Date

  • December 12, 2003

Published In

Volume / Issue

  • 115 / 6

Start / End Page

  • 727 - 738

PubMed ID

  • 14675537

Pubmed Central ID

  • 14675537

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(03)00939-5

Language

  • eng

Conference Location

  • United States