HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation

Arnaud Parcellier, Elise Schmitt, Sandeep Gurbuxani, Daphné Seigneurin-Berny, Alena Pance, Aurélie Chantôme, Stéphanie Plenchette, Saadi Khochbin, Eric Solary, Carmen Garrido

Research output: Contribution to journalArticlepeer-review


HSP27 is an ATP-independent chaperone that confers protection against apoptosis through various mechanisms, including a direct interaction with cytochrome c. Here we show that HSP27 overexpression in various cell types enhances the degradation of ubiquitinated proteins by the 26S proteasome in response to stressful stimuli, such as etoposide or tumor necrosis factor alpha (TNF-alpha). We demonstrate that HSP27 binds to polyubiquitin chains and to the 26S proteasome in vitro and in vivo. The ubiquitin-proteasome pathway is involved in the activation of transcription factor NF-kappaB by degrading its main inhibitor, I-kappaBalpha. HSP27 overexpression increases NF-kappaB nuclear relocalization, DNA binding, and transcriptional activity induced by etoposide, TNF-alpha, and interleukin 1beta. HSP27 does not affect I-kappaBalpha phosphorylation but enhances the degradation of phosphorylated I-kappaBalpha by the proteasome. The interaction of HSP27 with the 26S proteasome is required to activate the proteasome and the degradation of phosphorylated I-kappaBalpha. A protein complex that includes HSP27, phosphorylated I-kappaBalpha, and the 26S proteasome is formed. Based on these observations, we propose that HSP27, under stress conditions, favors the degradation of ubiquitinated proteins, such as phosphorylated I-kappaBalpha. This novel function of HSP27 would account for its antiapoptotic properties through the enhancement of NF-kappaB activity.
Original languageEnglish
Pages (from-to)5790-802
Number of pages13
JournalMolecular and cellular biology
Issue number16
Publication statusPublished - Aug 2003


  • Animals
  • Apoptosis
  • Chromatography, Gel
  • Cysteine Endopeptidases/metabolism
  • Cytochrome c Group/metabolism
  • Dose-Response Relationship, Drug
  • Etoposide/pharmacology
  • Genes, Reporter
  • Genetic Vectors
  • Glutathione Transferase/metabolism
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Humans
  • I-kappa B Proteins/metabolism
  • Immunoblotting
  • Interleukin-1/metabolism
  • Models, Biological
  • Molecular Chaperones
  • Multienzyme Complexes/metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B/metabolism
  • Neoplasm Proteins/metabolism
  • Peptide Hydrolases/metabolism
  • Phosphorylation
  • Precipitin Tests
  • Proteasome Endopeptidase Complex
  • Rats
  • Time Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha/metabolism
  • U937 Cells
  • Ubiquitin/metabolism


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