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

Publication ,  Journal Article
Kawaguchi, Y; Kovacs, JJ; McLaurin, A; Vance, JM; Ito, A; Yao, TP
Published in: Cell
December 12, 2003

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.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 12, 2003

Volume

115

Issue

6

Start / End Page

727 / 738

Location

United States

Related Subject Headings

  • Ubiquitin
  • Stress, Physiological
  • Protein Transport
  • Protein Folding
  • Protein Binding
  • Parkinson Disease
  • Organelles
  • Microtubules
  • Macromolecular Substances
  • Lewy Bodies
 

Citation

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Kawaguchi, Y., Kovacs, J. J., McLaurin, A., Vance, J. M., Ito, A., & Yao, T. P. (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell, 115(6), 727–738. https://doi.org/10.1016/s0092-8674(03)00939-5
Kawaguchi, Yoshiharu, Jeffrey J. Kovacs, Adam McLaurin, Jeffery M. Vance, Akihiro Ito, and Tso Pang Yao. “The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress.Cell 115, no. 6 (December 12, 2003): 727–38. https://doi.org/10.1016/s0092-8674(03)00939-5.
Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell. 2003 Dec 12;115(6):727–38.
Kawaguchi, Yoshiharu, et al. “The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress.Cell, vol. 115, no. 6, Dec. 2003, pp. 727–38. Pubmed, doi:10.1016/s0092-8674(03)00939-5.
Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell. 2003 Dec 12;115(6):727–738.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 12, 2003

Volume

115

Issue

6

Start / End Page

727 / 738

Location

United States

Related Subject Headings

  • Ubiquitin
  • Stress, Physiological
  • Protein Transport
  • Protein Folding
  • Protein Binding
  • Parkinson Disease
  • Organelles
  • Microtubules
  • Macromolecular Substances
  • Lewy Bodies