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Molecular and Cellular Biology, August 2003, p. 5790-5802, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5790-5802.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

HSP27 Is a Ubiquitin-Binding Protein Involved in I-{kappa}B{alpha} Proteasomal Degradation

Arnaud Parcellier,1 Elise Schmitt,1 Sandeep Gurbuxani,1 Daphné Seigneurin-Berny,2 Alena Pance,1 Aurélie Chantôme,1 Stéphanie Plenchette,1 Saadi Khochbin,2 Eric Solary,1 and Carmen Garrido1*

INSERM U517, UFR Médecine et Pharmacie, 21033 Dijon INSERM U309, Institut Albert Bonniot, Faculté de Médecine, 38706 La Tronche Cedex, France2

Received 9 January 2003/ Returned for modification 19 February 2003/ Accepted 12 May 2003

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-{kappa}B by degrading its main inhibitor, I-{kappa}B{alpha}. HSP27 overexpression increases NF-{kappa}B nuclear relocalization, DNA binding, and transcriptional activity induced by etoposide, TNF-{alpha}, and interleukin 1ß. HSP27 does not affect I-{kappa}B{alpha} phosphorylation but enhances the degradation of phosphorylated I-{kappa}B{alpha} by the proteasome. The interaction of HSP27 with the 26S proteasome is required to activate the proteasome and the degradation of phosphorylated I-{kappa}B{alpha}. A protein complex that includes HSP27, phosphorylated I-{kappa}B{alpha}, 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-{kappa}B{alpha}. This novel function of HSP27 would account for its antiapoptotic properties through the enhancement of NF-{kappa}B activity.

* Corresponding author. Mailing address: INSERM U517, Faculté de Médecine, 7 Blvd. Jeanne d'Arc, 21033 Dijon, France. Phone: 33 3 80 39 32 84. Fax: 33 3 80 39 34 34. E-mail: cgarrido{at}u-bourgogne.fr.

Molecular and Cellular Biology, August 2003, p. 5790-5802, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5790-5802.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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