Khochbin S, Chabanas A, Lawrence J J
Unité INSERM 309, Département de Recherche Fondamentale, CEN-Grenoble, France.
Exp Cell Res. 1988 Dec;179(2):565-74. doi: 10.1016/0014-4827(88)90294-7.
Among the early events of induced differentiation of murine erythroleukemia cells that we studied was the variations of cell distribution in the cell cycle as a function of the time of induction. Flow-cytofluorimetry measurements of DNA content and BrdU incorporation allowed for a precise determination of the variations of the cell cycle parameters. Cells underwent a transient arrest in both G1 and G2 + M between 6 to 16 h of induction. The progression of the cells through S phase seems not to be affected during this period. After this time cells escaped from G1 and reentered the S phase. We described previously [S. Khochbin et al. (1988) J. Mol. Biol. 200, 55-64], that p53 decreased continuously during the induction of MELC and remained at a steady-state level after 18 to 20 h of induction. In order to look for a possible redistribution of the protein along the cell cycle during the induction process, we measured the accumulation of the protein along the cell cycle. In noninduced cells there were four steps in the accumulation of the protein throughout the cell cycle: the amount of p53 was constant during G1 and it increased as cells progressed through S phase, which is characterized by an increased accumulation at the G1/S transition and a more moderate accumulation during progression through the rest of the S phase. A constant level in G2/M, approximately twice that obtained in G1, was achieved. There was no change in this distribution that correlated with the various modifications of the cell cycle in induced cells. It seems then, that p53 is associated neither with the progression of the cells in the S phase nor with the resumption of the DNA synthesis after the G1 block.
在我们研究的小鼠红白血病细胞诱导分化早期事件中，细胞周期中的细胞分布变化是诱导时间的函数。通过流式细胞荧光测定法测量DNA含量和BrdU掺入量，可以精确确定细胞周期参数的变化。在诱导6至16小时之间，细胞在G1期和G2 + M期均经历短暂停滞。在此期间，细胞通过S期的进程似乎未受影响。此后，细胞从G1期逸出并重新进入S期。我们之前描述过[S. Khochbin等人（1988年）《分子生物学杂志》200, 55 - 64]，在MELC诱导过程中p53持续下降，并在诱导18至20小时后保持在稳态水平。为了寻找诱导过程中该蛋白在细胞周期中的可能重新分布，我们测量了该蛋白在细胞周期中的积累情况。在未诱导的细胞中，该蛋白在整个细胞周期中的积累有四个阶段：p53的量在G1期保持恒定，随着细胞进入S期而增加，其特征是在G1/S转换处积累增加，在S期其余阶段积累较为平缓。在G2/M期达到恒定水平，约为G1期的两倍。在诱导细胞中，这种分布与细胞周期的各种变化没有相关性。那么，似乎p53既不与细胞在S期的进程相关，也不与G1期阻滞后DNA合成的恢复相关。
