Gene interactions and pathways from curated databases and text-mining
EMBO J 2001, PMID: 11707401

Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53.

King, F W; Wawrzynow, A; Höhfeld, J; Zylicz, M

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.

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Text Mining Data

p53 → Hsp40: " Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53 "

Hsc70 → Hsp40: " Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53 "

Hsp90 → Hsp40: " Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53 "

Hsc70 ⊣ Hsp90: " 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 "

Hsp40 ⊣ Hsp90: " 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 "

p53R175H → Hsc70: " The conformational mutant p53R175H can form a stable heterocomplex with Hsp90 only in the presence of Hsc70 , Hsp40, Hop and ATP "

p53R175H → Hsp40: " The conformational mutant p53R175H can form a stable heterocomplex with Hsp90 only in the presence of Hsc70, Hsp40 , Hop and ATP "

Manually curated Databases

  • IRef Hprd Interaction: TP53 — HSP90AB1 (in vitro)
  • IRef Hprd Interaction: TP53 — HSP90AB1 (in vivo)
  • IRef Ophid Interaction: TP53 — HSP90AB1 (aggregation, confirmational text mining)
In total, 1 gene pairs are associated to this article in curated databases