Buquet-Fagot C, Lallemand F, Charollais R H, Mester J
INSERM U55, Hôpital Saint-Antoine, Paris, France.
J Cell Physiol. 1996 Mar;166(3):631-6. doi: 10.1002/(SICI)1097-4652(199603)166:3<631::AID-JCP18>3.0.CO;2-9.
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.
在化学转化的小鼠成纤维细胞BP - A31中，视网膜母细胞瘤蛋白（pRB）在静止期处于低磷酸化状态，在血清刺激约6小时后变为高磷酸化。如果丁酸钠与血清一起添加或在血清刺激后3小时内添加，则pRb的磷酸化被阻断。血清刺激3小时后添加放线菌素D并不能阻止pRb磷酸化，但它逆转了丁酸钠的抑制作用。这些观察结果表明，丁酸钠通过开启编码阻止高磷酸化pRb积累的蛋白质的基因表达而起作用。这种丁酸钠诱导的抑制剂可能会干扰细胞周期蛋白依赖性激酶对pRb的磷酸化。与单独使用血清相比，在丁酸钠存在的情况下用血清处理静止的BP - A31细胞会导致Waf1/CIP1 mRNA（编码一种细胞周期蛋白依赖性激酶抑制蛋白）的细胞含量增加，这表明p21Waf1/CIP1可能发挥作用。相比之下，丝裂原活化蛋白激酶（已被证明可磷酸化pRb的酶）在BP - A31细胞中持续活跃，并且其活性在与丁酸钠孵育≤3小时后没有受到显著影响。
