Titre
Heat shock protein (Hsp) 40 mutants inhibit Hsp70 in mammalian cells.
Type
article
Institution
Externe
Périodique
Auteur(s)
Michels, A.A.
Auteure/Auteur
Kanon, B.
Auteure/Auteur
Bensaude, O.
Auteure/Auteur
Kampinga, H.H.
Auteure/Auteur
Liens vers les personnes
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
1999
Volume
274
Numéro
51
Première page
36757
Dernière page/numéro d’article
36763
Peer-reviewed
Oui
Langue
anglais
Résumé
Heat shock protein (Hsp) 70 and Hsp40 expressed in mammalian cells had been previously shown to cooperate in accelerating the reactivation of heat-denatured firefly luciferase (Michels, A. A., Kanon, B., Konings, A. W. T., Ohtsuka, K., Bensaude, O., and Kampinga, H. H. (1997) J. Biol. Chem. 272, 33283-33289). We now provide further evidence for a functional interaction between Hsp70 and the J-domain of Hsp40 with denatured luciferase resulting in reactivation of heat-denatured luciferase within living mammalian cells. The stimulating effect of Hsp40 on the Hsp70-mediated refolding is lost when the proteins cannot interact as accomplished by their expression in different intracellular compartments. Likewise, the cooperation between Hsp40 and Hsp70 is lost by introduction of a point mutation in the conserved HPD motif of the Hsp40 J-domain or by deletion of the four C-terminal amino acids of Hsp70 (EEVD motif). Most strikingly, co-expression of a truncated protein restricted to the J-domain of Hsp40 had a dominant negative effect on Hsp70-facilitated luciferase reactivation. Taken together, these experiments indicate for the first time that the Hsp70/Hsp40 chaperones functionally interact with a heat-denatured protein within mammalian cells. The dominant negative effect of the Hsp40 J-domain on the activity of Hsp70 demonstrates the importance of J-domain-containing proteins in Hsp70-dependent processes.
PID Serval
serval:BIB_8F6F3B854288
PMID
Open Access
Oui
Date de création
2008-07-28T15:08:04.719Z
Date de création dans IRIS
2025-05-21T02:43:19Z