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Updated: Jul 6, 2026

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
06:51

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay

Published on: July 21, 2021

The human TPR protein TTC4 is a putative Hsp90 co-chaperone which interacts with CDC6 and shows alterations in

Gilles Crevel1, Dorothy Bennett, Sue Cotterill

  • 1Department of Basic Medical Sciences, St. Georges Hospital Medical School, London, United Kingdom.

Plos One
|March 6, 2008
PubMed
Abstract

Insights

The TTC4 protein, linked to breast cancer and melanoma, interacts with HSP90 and CDC6. Mutations in TTC4 disrupt its interaction with CDC6, potentially influencing cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • The human TTC4 protein contains tetratricopeptide repeat (TPR) motifs.
  • TTC4 gene localization is linked to breast cancer.
  • TTC4 mutations are observed in melanoma cell lines, suggesting a role in disease progression.

Purpose of the Study:

  • To investigate the cellular localization and interaction partners of the TTC4 protein.
  • To explore the functional significance of TTC4 in the context of malignant melanoma.
  • To determine if TTC4 mutations affect its interaction with known partners.

Main Methods:

  • Immunofluorescence to determine cellular localization.
  • Co-immunoprecipitation assays to identify interaction partners (HSP90, HSP70, CDC6).
  • Analysis of TTC4 protein levels in melanoma and other tumor cell lines.
  • Assessment of mutant TTC4 protein interactions with CDC6.

Main Results:

  • TTC4 is a nucleoplasmic protein.
  • TTC4 interacts with HSP90, HSP70, and the replication protein CDC6.
  • TTC4 protein levels are elevated in malignant melanoma and other tumor cell lines.
  • TTC4 mutations identified in patients disrupt the interaction with CDC6.

Conclusions:

  • TTC4 functions as an HSP90 co-chaperone, linking HSP90 activity to DNA replication.
  • Disruption of TTC4 interactions with CDC6 or other client proteins may contribute to malignant cell development.
  • TTC4 is a potential therapeutic target in cancers associated with its dysfunction.

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