[Heat shock protein 70 binding protein 1 induces enhanced apoptotic response against anticancer drugs in tumor cells].
HspBP1 was originally identified and characterized as a novel Hsp70/Hsc70-interacting protein that inhibited the Hsp70/Hsc70 chaperone activity. In this respect, Hsps have been shown to influence cell-death pathway through the interaction with key components of the apoptotic machinery. In this report, we have examined the effect of HspBP1 overexpression on the sensitivity of tumor cells to anticancer drug-induced apoptotic response. Analysis with HspBP1 deletion mutant genes showed that C-terminus 47 amino acid residues were essential for the specific interaction of HspBP1 with Hsp70/Hsc70. Overexpression of HspBP1 induced enhanced apoptotic response against anticancer drugs, but HspBP1 lacking C-terminus 47 amino acid residues did not. These results support the notion that inhibition of the function of Hsp70 enhances the therapeutic efficacy of chemotherapy.
Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University.
Susumu
S
Tanimura
Michiaki
M
Kohno
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; C116331:HSPBP1 protein, human