The gene for the rat heat-shock cognate, hsc70, can suppress oncogene-mediated transformation.
In cells transformed by mutant mouse p53 plus ras, the former protein is found to be complexed with the heat-shock protein cognate hsc70. To determine whether hsc70 can directly affect neoplastic transformation, nonestablished rat embryo fibroblasts (REF) were transfected with rat genomic hsc70 DNA in conjunction with various oncogenes. We report here that the hsc70 gene could efficiently suppress focus induction by mutant p53 plus ras, as well as by myc plus ras. No inhibitory effect of hsc70 was detectable in assays monitoring the ability of REF to be immortalized by mutant p53, arguing against a nonspecific deleterious effect of the hsc70 genomic clone on REF survival and proliferation. Lines generated in the presence of the hsc70 plasmid produced augmented levels of hsc70. Plasmids encoding only short NH2-terminal fragments of hsc70 could also, in some cases, partially reduce oncogene-mediated focus formation. However, a maximal inhibitory effect required the production of a functional hsc70 protein. The data presented here raise the possibility that hsc70 may be directly involved in the modulation of oncogene-mediated transformation.
Yehiely
F
F
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Oren
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats / Q000235:genetics*; D011916:Rats, Inbred F344 / Q000196:embryology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; C494373:Hspa8 protein, rat; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53