Hsp90α Chaperones Large C-Terminally Extended Proteolytic Intermediates in the MHC Class I Antigen Processing Pathway

Jun Kunisawa, Nilabh Shastri

Research output: Contribution to journalArticlepeer-review

Abstract

Intracellular proteins are degraded in the antigen processing pathway to generate peptide-loaded MHC I complexes (pMHC I) for immune surveillance. The characteristics of the final pMHC I are clear but those of their precursors and their potential binding partners remain poorly defined. By using a unique method to biochemically detect preprocessed ovalbumin-derived antigenic peptides, we find that cells generate large, C-terminally extended proteolytic intermediates that are associated with the α isotype of hsp90 chaperone. Knockdown of hsp90α expression by siRNA resulted in the loss of these intermediates and decreased presentation of the final pMHC I on the cell surface. Generation of pMHC I was also inhibited by knockdown of the cochaperone CHIP that interacts with heat shock proteins, ubiquitinates their clients, and delivers them to the proteasome. Thus, hsp90α can serve as a chaperone for precursors of pMHC I at an early stage in the antigen processing pathway.

Original languageEnglish (US)
Pages (from-to)523-534
Number of pages12
JournalImmunity
Volume24
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Hsp90α Chaperones Large C-Terminally Extended Proteolytic Intermediates in the MHC Class I Antigen Processing Pathway'. Together they form a unique fingerprint.

Cite this