DOI: 10.1101/gad.436407. HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates

HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates

10.1101/gad.436407

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

A cellular defense mechanism counteracts the deleterious effects of misfolded protein accumulation by eliciting a stress response. The cytoplasmic deacetylase HDAC6 (histone deacetylase 6) was previously shown to be a key element in this response by coordinating the clearance of protein aggregates through aggresome formation and their autophagic degradation. Here, for the first time, we demonstrate that HDAC6 is involved in another crucial cell response to the accumulation of ubiquitinated protein aggregates, and unravel its molecular basis. Indeed, our data show that HDAC6 senses ubiquitinated cellular aggregates and consequently induces the expression of major cellular chaperones by triggering the dissociation of a repressive HDAC6/HSF1 (heat-shock factor 1)/HSP90 (heat-shock protein 90) complex and a subsequent HSF1 activation. HDAC6 therefore appears as a master regulator of the cell protective response to cytotoxic protein aggregate formation.

Bibliography

Boyault, C., Zhang, Y., Fritah, S., Caron, C., Gilquin, B., Kwon, S. H., Garrido, C., Yao, T.-P., Vourcâh, C., Matthias, P., & Khochbin, S. (2007). HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes & Development, 21(17), 2172â2181.

Authors 11

Cyril Boyault (first)
Yu Zhang (additional)
Sabrina Fritah (additional)
Cécile Caron (additional)
Benoit Gilquin (additional)
So Hee Kwon (additional)
Carmen Garrido (additional)
Tso-Pang Yao (additional)
Claire Vourc’h (additional)
Patrick Matthias (additional)
Saadi Khochbin (additional)

References 40 Referenced 319

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Dates

Type	When
Created	17 years, 11 months ago (Sept. 4, 2007, 1:33 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:09 p.m.)
Indexed	17 hours, 44 minutes ago (Aug. 30, 2025, 12:50 p.m.)
Issued	17 years, 11 months ago (Sept. 1, 2007)
Published	17 years, 11 months ago (Sept. 1, 2007)
Published Online	17 years, 11 months ago (Sept. 4, 2007)
Published Print	17 years, 11 months ago (Sept. 1, 2007)

Funders 0

None

BibTeX

@article{Boyault_2007, title={HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates}, volume={21}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.436407}, DOI={10.1101/gad.436407}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Boyault, Cyril and Zhang, Yu and Fritah, Sabrina and Caron, Cécile and Gilquin, Benoit and Kwon, So Hee and Garrido, Carmen and Yao, Tso-Pang and Vourc’h, Claire and Matthias, Patrick and Khochbin, Saadi}, year={2007}, month=sep, pages={2172–2181} }

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