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

Cyril Boyault, Yu Zhang, Sabrina Fritah, Cécile Caron, Benoit Gilquin, Hee Kwon So, Carmen Garrido, Tso Pang Yao, Claire Vourc'h, Patrick Matthias, Saadi Khochbin

Research output: Contribution to journalArticle

226 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2172-2181
Number of pages10
JournalGenes and Development
Volume21
Issue number17
DOIs
Publication statusPublished - 2007 Sep 1

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Histone Deacetylases
HSP90 Heat-Shock Proteins
Ubiquitinated Proteins
Response Elements
Shock
Hot Temperature
Protein Aggregates
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

Boyault, C., Zhang, Y., Fritah, S., Caron, C., Gilquin, B., So, H. K., ... Khochbin, S. (2007). HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes and Development, 21(17), 2172-2181. https://doi.org/10.1101/gad.436407
Boyault, Cyril ; Zhang, Yu ; Fritah, Sabrina ; Caron, Cécile ; Gilquin, Benoit ; So, Hee Kwon ; Garrido, Carmen ; Yao, Tso Pang ; Vourc'h, Claire ; Matthias, Patrick ; Khochbin, Saadi. / HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. In: Genes and Development. 2007 ; Vol. 21, No. 17. pp. 2172-2181.
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Boyault, C, Zhang, Y, Fritah, S, Caron, C, Gilquin, B, So, HK, Garrido, C, Yao, TP, Vourc'h, C, Matthias, P & Khochbin, S 2007, 'HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates', Genes and Development, vol. 21, no. 17, pp. 2172-2181. https://doi.org/10.1101/gad.436407

HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. / Boyault, Cyril; Zhang, Yu; Fritah, Sabrina; Caron, Cécile; Gilquin, Benoit; So, Hee Kwon; Garrido, Carmen; Yao, Tso Pang; Vourc'h, Claire; Matthias, Patrick; Khochbin, Saadi.

In: Genes and Development, Vol. 21, No. 17, 01.09.2007, p. 2172-2181.

Research output: Contribution to journalArticle

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