Sodium butyrate inhibits the phosphorylation of the retinoblastoma gene product in mouse fibroblasts by a transcription-dependent mechanism.
In the chemically transformed mouse fibroblasts BP-A31, the retinoblastoma protein (pRB) is hypophosphorylated at quiescence and becomes hyperphosphorylated after approximately 6 h of serum stimulation. Phosphorylation of pRb was blocked if sodium butyrate was added together with serum or within 3 h afterwards. Actinomycin D added 3 h after serum stimulation did not prevent pRb phosphorylation, but it reversed the inhibitory effect of butyrate. These observations indicate that sodium butyrate acts by turning on the expression of gene(s) coding for proteins which prevent the accumulation of hyperphosphorylated pRb. Such butyrate-induced inhibitor(s) may interfere with the phosphorylation of pRb by cyclin-dependent kinases. Treatment of quiescent BP-A31 cells with serum in the presence of sodium butyrate has led to an increased cell content of the Waf1/CIP1 mRNA (coding for a cyclin-dependent) kinase inhibitory protein) compared with serum alone, suggesting a possible role of p21Waf1/CIP1. In contrast, the mitogen activated protein kinase (enzyme which has been shown to phosphorylate pRb) was constitutively active in BP-A31 cells, and its activity was not significantly affected by a < or = 3h incubation with sodium butyrate.
Buquet-Fagot
C
C
INSERM U55, Hôpital Saint-Antoine, Paris, France.
Lallemand
F
F
Charollais
R H
RH
Mester
J
J
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D002087:Butyrates; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D020148:Butyric Acid; D003609:Dactinomycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases