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Author Notes:

To whom correspondence should be addressed: Dept. of Pediatrics, Emory University School of Medicine, 2015 Uppergate Dr., Atlanta, GA 30322. Tel.: 404-727-1746; Fax: 404-727-9223; E-mail: bsong4@emory.edu.

We thank Dr. Garrison Fathman (Stanford University, Stanford, CA), Dr. Harm Kampinga (University of Groningen, The Netherlands), Dr. Danny Manor (Case Western Reserve University, Cleveland, OH), and Dr. Len Neckers (NCI, National Institutes of Health, Bethesda, MD) for the generous gift of expression vectors for ubiquitin, Hsp70, Hsc70, and Hsp90, respectively.

We are grateful to the Emory Proteomics Core Service Center for mass spectral analyses.

We thank Hamish Young for helpful discussions, advice, and critically reading the manuscript.


Research Funding:

This work was supported by the Campbell Foundation Award, Emory University Research Committee Award, Emory Egleston Children's Research Center Award, and Emory Center for AIDS Research Award P30AI050409 (to B. S.), and partially supported by the Korea Research Council of Fundamental Science and Technology Award M10642040003 and National Research Foundation of Korea Award M10503010002 (to K.-S. K.).


  • Apoptosis
  • E3 Ubiquitin Ligase
  • ER Stress
  • HIV
  • Protein Folding
  • Ubiquitination
  • Chaperone
  • Hsp70
  • TRIM

Hsp70 Interacts with the Retroviral Restriction Factor TRIM5α and Assists the Folding of TRIM5α


Journal Title:

Journal of Biological Chemistry


Volume 285, Number 10


, Pages 7827-7837

Type of Work:

Article | Final Publisher PDF


Tripartite motif (TRIM) protein TRIM5α has been shown to restrict human immunodeficiency virus, type 1 infection in Old World monkey cells at the early post-entry step by poorly understood mechanisms. Currently, the physiological function of TRIM5α is not known. In this study, we showed that transiently overexpressed TRIM5α causes a morphological change in HEK293T cells. A proteomics analysis of the protein complexes that were pulled down with hemagglutinin-tagged TRIM5α suggested that the heat shock protein 70 (Hsp70) may serve as a TRIM5α-binding partner. The interaction between Hsp70 and TRIM5α was confirmed by co-localization and co-immunoprecipitation assays. Co-expression of Hsp70 reversed the TRIM5α-induced morphological change in HEK293T cells. Another heat shock protein Hsc70 also bound to TRIM5α, but unlike Hsp70, Hsc70 was not able to reverse the TRIM5α-induced morphological change, suggesting that Hsp70 specifically reverses the morphological change caused by TRIM5α. Studies using a series of TRIM5α deletion mutants demonstrate that, although the PRYSPRY domain is critical for binding to Hsp70, the entire TRIM5α structure is necessary to induce the morphological change of cells. When the ATPase domain of Hsp70 was mutated, the mutated Hsp70 could not counteract the morphological change induced by TRIM5α, indicating that the catalytic activity of Hsp70 protein is important for this function. Co-expression of Hsp70 elevated the levels of TRIM5α in the detergent-soluble fraction with a concomitant decrease in the detergent-insoluble fraction. Together these results suggest that Hsp70 plays critical roles in the cellular management against the TRIM5α-induced cellular insults.

Copyright information:

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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