Rao G N, Church R L, Davidson J N
Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322.
FEBS Lett. 1988 May 9;232(1):238-42. doi: 10.1016/0014-5793(88)80424-1.
We have studied the regulation of expression of the carbamoyl-phosphate synthetase II-aspartate transcarbamylase-dihydroorotase gene in F9 teratocarcinoma cells during their differentiation into parietal endoderm cells by induction with a combination of retinoic acid and dibutyryl cyclic AMP. Steady-state levels of CAD mRNA decreased by 7-fold in F9 cells following 120 h of retinoic acid and dibutyryl cyclic AMP induction as compared to levels in uninduced cells. Conversely, no apparent changes were found in the steady-state levels of beta-actin mRNA between induced and uninduced cells. Despite a 7-fold decrease in the steady-state levels of CAD mRNA, its rate of transcription remained the same between induced and uninduced cells, indicating a role for posttranscriptional mechanisms for its down regulation during retinoic acid- and dibutyryl cyclic AMP-induced differentiation of F9 cells. The cellular growth rate of F9 cells as determined by [3H]thymidine uptake and parallel cell counting decreased markedly during their induction with retinoic acid and dibutyryl cyclic AMP. Taken together, it is apparent that the expression of the CAD gene is cell-growth-dependent and its regulation in this system is at the posttranscriptional level.
我们研究了在视黄酸和二丁酰环磷酸腺苷的联合诱导下，F9畸胎癌细胞分化为滋养层内胚层细胞过程中氨甲酰磷酸合成酶II-天冬氨酸转氨甲酰酶-二氢乳清酸酶基因表达的调控。与未诱导细胞相比，视黄酸和二丁酰环磷酸腺苷诱导120小时后，F9细胞中CAD mRNA的稳态水平下降了7倍。相反，诱导细胞和未诱导细胞之间β-肌动蛋白mRNA的稳态水平没有明显变化。尽管CAD mRNA的稳态水平下降了7倍，但诱导细胞和未诱导细胞之间其转录速率保持不变，这表明在视黄酸和二丁酰环磷酸腺苷诱导的F9细胞分化过程中，转录后机制在其下调中起作用。通过[3H]胸苷摄取和平行细胞计数测定，F9细胞在用视黄酸和二丁酰环磷酸腺苷诱导期间，其细胞生长速率显著下降。综上所述，很明显CAD基因的表达依赖于细胞生长，并且在该系统中其调控处于转录后水平。
