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Co‐chaperones Bag‐1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild‐type or mutant p53
Author(s) -
King Frank W.,
Wawrzynow Alicja,
Höhfeld Jörg,
Zylicz Maciej
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.22.6297
Subject(s) - biology , hsp90 , mutant , hop (telecommunications) , humulus lupulus , wild type , chaperone (clinical) , microbiology and biotechnology , genetics , heat shock protein , gene , medicine , pathology , computer network , pepper , computer science , horticulture
Using highly purified proteins, we have identified intermediate reactions that lead to the assembly of molecular chaperone complexes with wild‐type or mutant p53R175H protein. Hsp90 possesses higher affinity for wild‐type p53 than for the conformational mutant p53R175H. The presence of Hsp90 in a complex with wild‐type p53 inhibits the binding of Hsp40 and Hsc70 to p53, consequently preventing the formation of wild‐type p53–multiple chaperone complexes. The conformational mutant p53R175H can form a stable heterocomplex with Hsp90 only in the presence of Hsc70, Hsp40, Hop and ATP. The anti‐apoptotic factor Bag‐1 can dissociate Hsp90 from a pre‐ assembled complex wild‐type p53 protein, but it cannot dissociate a pre‐assembled p53R175H–Hsp40–Hsc70–Hop–Hsp90 heterocomplex. The results presented here provide possible molecular mechanisms that can help to explain the observed in vivo role of molecular chaperones in the stabilization and cellular localization of wild‐type and mutant p53 protein.