Induction of 68,000-dalton heat shock proteins by cyclopentenone prostaglandins. Its association with prostaglandin-induced G1 block in cell cycle progression.
Cyclopentenone prostaglandins (PGs) such as PGA2 and delta 12-PGJ2 act specifically on cells in the G1 phase and induce block of cell cycle progression (Ohno, K., Sakai, T., Fukushima, M., Narumiya, S., and Fujiwara, M. (1988) J. Pharmacol. Exp. Ther. 245, 294-298). In this study, we characterized proteins induced by these PGs in HeLa S3 cells of synchronized growth and examined its association with the cell cycle block. HeLa S3 cells transiently expressed two 68-kDa proteins of isoelectric points of 5.5 and 5.6 in the G1 phase of cell cycle. When G1-enriched cells were incubated with either PGA2 or delta 12-PGJ2, synthesis of these proteins was markedly enhanced. Enhancement by delta 12-PGJ2 was persistent and irreversible, whereas that by PGA2 was reversible. delta 12-PGJ2 also enhanced the synthesis of two additional 68-kDa proteins with isoelectric points of 5.8 and 5.9. On two-dimensional gel electrophoresis, these proteins overlapped exactly with the 68-kDa heat shock proteins induced in cells treated at 43 degrees C for 90 min. They were also indistinguishable from the heat shock proteins in limited proteolysis. When delta 12-PGJ2 was incubated with G2/M phase cells, it induced only a small and transient increase in the 68-kDa proteins. These results suggest that cyclopentenone PGs extensively induce 68-kDa heat shock proteins in the G1 phase HeLa S3 cells and this induction is closely associated with the G1 block of cell cycle progression caused by these PGs.
Ohno
K
K
Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.
Fukushima
M
M
Fujiwara
M
M
Narumiya
S
S
D002453:Cell Cycle / Q000187:drug effects*; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010449:Peptide Mapping; D011453:Prostaglandins / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011453:Prostaglandins; D008715:Methionine