Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family

Keith Alvares*, Alejandro Carrillo, Pau M. Yuan, Hiroko Kawano, Richard I. Morimoto, Janardan K. Reddy

*Corresponding author for this work

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluated. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site.

Original languageEnglish (US)
Pages (from-to)5293-5297
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number14
DOIs
StatePublished - 1990

Keywords

  • Drug-binding protein
  • Peroxisomes

ASJC Scopus subject areas

  • General

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