RGD Reference Report - HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation. - Rat Genome Database

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

Authors: Parcellier, A  Schmitt, E  Gurbuxani, S  Seigneurin-Berny, D  Pance, A  Chantome, A  Plenchette, S  Khochbin, S  Solary, E  Garrido, C 
Citation: Parcellier A, etal., Mol Cell Biol 2003 Aug;23(16):5790-802.
RGD ID: 1304417
Pubmed: PMID:12897149   (View Abstract at PubMed)
PMCID: PMC166315   (View Article at PubMed Central)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  TAS 1304417 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
proteasome complex  IDA 1304417 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ubiquitin binding  IDA 1304417 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspb1  (heat shock protein family B (small) member 1)


Additional Information