Retinoylation of proteins in leukemia, embryonal carcinoma, and normal kidney cell lines: differences associated with differential responses to retinoic acid.
In HL60 cells a nuclear protein of Mr 55,000 is retinoylated, with the formation of a thioester bond. To gain further knowledge on the role of retinoylation we studied it in cell lines with varied responses to retinoic acid (RA). Compared to HL60 the extent of retinoylation (mol/cell) was about fivefold higher in HL60/MRI, a mutant which is more sensitive to RA than HL60. Retinoylation occurred to the same extent and at similar rates in HL60 and in HL60/RA-res, a mutant resistant to differentiation by RA. One-dimensional polyacrylamide gel electrophoresis patterns for the three HL60 cell lines were similar. However, two-dimensional polyacrylamide gel electrophoresis patterns of the three HL60 cell lines were distinct. While we saw the same major retinoylated protein of Mr 55,000 in the three cell lines, the HL60/RA-res cells also contained a high level of a protein with the same Mr and a lower pI. The extent of retinoylation was greater in the RA-sensitive embryonal carcinoma cell line, PCC4.aza1R, than in a RA-resistant cell line, PCC4.(RA)-2. One-dimensional polyacrylamide gel electrophoresis patterns of retinoylated proteins of the embryonal carcinoma cell lines were different from HL60 and from each other. The retinoylation pattern of the normal canine kidney cell line (MDCK) was different from either HL60 or the embryonal carcinoma cells. These results showed the retinoylation was widespread and that the response to RA of different cell types may depend on the retinoylation of specific proteins.
Takahashi
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Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Breitman
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TR
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004351:Drug Resistance / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D008970:Molecular Weight; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D013724:Teratoma / Q000188:drug therapy / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014212:Tretinoin