Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family.
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 eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site.
Alvares
K
K
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
Carrillo
A
A
Yuan
P M
PM
Kawano
H
H
Morimoto
R I
RI
Reddy
J K
JK
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002846:Chromatography, Affinity; D002994:Clofibrate / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000302:isolation & purification; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D012156:Reticulocytes / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D002994:Clofibrate