Hofbauer R, Denhardt D T
Institut für Molekularbiologie, Universität Wein, Vienna, Austria.
Crit Rev Eukaryot Gene Expr. 1991;1(4):247-300.
We have reviewed here genes whose expression may vary during the "cell cycle" and we discuss the underlying regulatory mechanisms. Given a correlation between the cell cycle and expression of a particular gene, the question arises whether that gene regulates the cycle, whether the cycle regulates that gene, or whether the correlation is simply the consequence that both the cell cycle and that gene respond to the same signal(s). Gene expression is regulated at diverse levels, and the relative importance of regulation at these different levels depends on which version of the cell cycle one has in mind; depending upon the context, the concept of the (higher eukaryote) cell cycle has a number of different operational meanings. Thus the first few divisions of the fertilized egg consist of successive S and M phases, with insignificant G1 and G2 phases, regulated entirely at the translational and post-translational level by the phosphorylation/dephosphorylation of p34cdc2 and the synthesis/degradation of one or more cyclins-keyed perhaps to the cytoplasm/nucleoplasm ratio and the completion of DNA replication. In contrast, cells stimulated to exit quiescence, (G0), require new gene transcription and changes in the post-transcriptional control of gene expression. Cells proliferating in a constant environment proceed directly from mitosis into G1 and are less dependent on (but not independent of) new transcription; here controls at the post-transcriptional and post-translational levels are more pronounced. In addition to regulation by p34cdc2, input from cell-specific growth factors or other extracellular signals is essential for most untransformed cells to continue through the cycle. Many transformed cells in contrast do not require exogenous signals and are altered in the way that key regulatory genes (e.g., p53, RB) are controlled. While cells of many lower eukaryotes appear capable of an indefinite number of cell cycles, the typical higher eukaryotic cell appears to have a limit on this number--untransformed, nonestablished vertebrate cells are usually mortal. For unknown reasons, established cell lines and certain embryonic or stem cells under the right conditions, are immortal and capable of indefinite proliferation. Apparently, the price paid to construct a differentiated multicellular organism is a limit on the number of cell divisions that the constituent somatic cells are capable of undergoing.
我们在此回顾了那些在“细胞周期”中表达可能会发生变化的基因，并探讨了其潜在的调控机制。鉴于细胞周期与特定基因的表达之间存在相关性，于是就出现了这样一个问题：该基因是否调控细胞周期，细胞周期是否调控该基因，或者这种相关性是否仅仅是细胞周期和该基因都对相同信号作出反应的结果。基因表达在多个层面受到调控，而这些不同层面调控的相对重要性取决于人们所设想的细胞周期的版本；根据具体情况，（高等真核生物的）细胞周期概念有许多不同的操作意义。因此，受精卵最初的几次分裂由连续的S期和M期组成，G1期和G2期不明显，完全在翻译和翻译后水平上通过p34cdc2的磷酸化/去磷酸化以及一种或多种细胞周期蛋白的合成/降解来调控，这可能与细胞质/核质比以及DNA复制的完成有关。相比之下，被刺激退出静止期（G0期）的细胞需要新的基因转录以及基因表达的转录后控制发生变化。在恒定环境中增殖的细胞直接从有丝分裂进入G1期，并且对新转录的依赖性较小（但并非不依赖）；这里转录后和翻译后水平的控制更为明显。除了受p34cdc2调控外，细胞特异性生长因子或其他细胞外信号的输入对于大多数未转化细胞继续完成细胞周期至关重要。相比之下，许多转化细胞不需要外源性信号，并且关键调控基因（如p53、RB）的控制方式发生了改变。虽然许多低等真核生物的细胞似乎能够进行无限次数的细胞周期，但典型的高等真核细胞似乎在这个次数上有一个限制——未转化的、未建立的脊椎动物细胞通常是有寿命的。出于未知原因，建立的细胞系以及某些在合适条件下的胚胎或干细胞是永生的，能够无限增殖。显然，构建一个分化的多细胞生物体所付出的代价是组成体细胞能够进行的细胞分裂次数受到限制。
