A role for paralog-specific sumoylation in histone deacetylase 1 stability

Simona Citro, Ellis Jaffray, Ronald T. Hay, Christian Seiser, Susanna Chiocca

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Histone deacetylase 1 (HDAC1) is an essential epigenetic regulator belonging to a highly conserved family of deacetylases. Increased HDAC1 activity and expression often correlates with neoplastic transformation. Here we show how specific modification of HDAC1 by SUMO1, but not by SUMO2, facilitates HDAC1 degradation. Our findings reveal that SUMO1, but not SUMO2, conjugation to HDAC1 promotes HDAC1 ubiquitination and degradation. This is suggested by the observation that in non-tumorigenic mammary epithelial cells HDAC1 is preferentially conjugated to SUMO1 leading to HDAC1 proteolysis, whereas in breast cancer cells HDAC1 is more conjugated to SUMO2, promoting HDAC1 protein stability. SUMO E3 ligases play an important role in paralog-specific conjugation; in particular, the SUMO E3 ligase PIASy, which is overexpressed in breast cancer cells, selectively promotes the conjugation of HDAC1 to SUMO2. Therefore, cell environment affects paralog-specific sumoylation of HDAC1, whose conjugation to SUMO1 but not to SUMO2 facilitates its protein turnover. Our findings uncover a role for paralog-specific sumoylation of HDAC1 whose significance is emphasized by the use of HDAC inhibitors as anticancer drugs.

Original languageEnglish
Pages (from-to)416-427
Number of pages12
JournalJournal of Molecular Cell Biology
Volume5
Issue number6
DOIs
Publication statusPublished - Dec 2013

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Histone Deacetylase 1
Sumoylation
Ubiquitin-Protein Ligases
Breast Neoplasms
Histone Deacetylase Inhibitors
Protein Stability
Ubiquitination

Keywords

  • Breast cancer
  • HDAC1
  • PIAS
  • SUMO
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

Cite this

A role for paralog-specific sumoylation in histone deacetylase 1 stability. / Citro, Simona; Jaffray, Ellis; Hay, Ronald T.; Seiser, Christian; Chiocca, Susanna.

In: Journal of Molecular Cell Biology, Vol. 5, No. 6, 12.2013, p. 416-427.

Research output: Contribution to journalArticle

Citro, Simona ; Jaffray, Ellis ; Hay, Ronald T. ; Seiser, Christian ; Chiocca, Susanna. / A role for paralog-specific sumoylation in histone deacetylase 1 stability. In: Journal of Molecular Cell Biology. 2013 ; Vol. 5, No. 6. pp. 416-427.
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