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细胞周期分子机制的成功探索——2001年诺贝尔生理及医学奖部分工作介绍 总被引:9,自引:0,他引:9
细胞周期是指连续分裂的细胞从一次有丝分裂结束到下一次有丝分裂完成所经历的整个序贯过程.在这一过程中,细胞的遗传物质(DNA)经过复制平均分配到两个子细胞中.细胞周期中每一事件都是有规律、精确地发生,并且在时间与空间上受到严格调控.细胞周期中最关键的三类调控因子是:cdc基因、周期蛋白依赖性激酶(CDKs)及细胞周期蛋白(cyclin).这些调控因子的发现对肿瘤学及发育生物学的发展都有重要的理论和实践意义. 相似文献
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细胞周期调控因子能通过影响细胞周期对植物细胞的生长、分裂和分化产生作用,进而调节植物的生长发育。本文综述了近几年来植物细胞周期调控因子中细胞周期蛋白(cyclin,CYC)、周期蛋白依赖激酶(cyclin-dependent kinase,CDK)等的作用机理及研究进展,阐述了各调控因子在植物生长发育过程中的作用。 相似文献
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细胞周期蛋白与CDI在细胞周期调控中的作用 总被引:2,自引:0,他引:2
在细胞周期调控研究中, 对cyclin-CDK在细胞周期调控中作用机制的认识已获得突破性进展. 近几年来, CDK抑制因子(CDIs)家族成员──p16和p21的分离和研究, 表明细胞周期蛋白(cyclin)与CDI在调节CDK活性方面形成了极为复杂的调控网络, 从而控制细胞的增殖与分化, 并与肿瘤的形成与发展相联系. 相似文献
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由高通量微阵列技术产生的数据集可以用于解释生物系统基因调控的未知机制.生物过程是动态的,所以很有必要关注某些条件下特异的基因调控子网络.细胞周期是一个基本的细胞过程,识别酵母的细胞周期特异调控子网是理解细胞周期过程的基础,并且有助于揭示其他细胞条件的基因调控机理.使用一个基因表达微分方程模型(GEDEM),从静态网络中识别了动态的细胞周期相关调控关系.与已经报道的细胞周期相关调控相互作用相比,该方法识别了更多的真实存在的条件特异调控关系,取得了比当前的方法更好的性能.在大数据集上,GEDEM 识别了具有高敏感性和特异性的调控子网.组合调控的深入分析显示,条件特异调控子网的转录因子之间的相关性呈现出比静态网络中转录因子相关性更强,这说明条件特异网络比静态网络更加接近真实情况.另外,GEDEM 方法还识别更多潜在的共调控转录因子. 相似文献
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细胞周期检查点在细胞遭遇DNA损伤因子的攻击或遇到营养缺乏等不利因素作用时,能够暂时阻止或减慢细胞周期的进程,是细胞在长期进化中发展起来的抵御DNA损伤的重要机制.不仅如此,最近的研究表明,在正常生理条件下,存在一种S期检查点,对DNA复制的速度进行调控.从分子水平而言,这种调控作用可能是通过一系列细胞周期调控蛋白如ATR、9-1-1复合体、Chk1、Cdc25A和CDK2等的作用来实现的.这种调节作用对细胞至关重要,它使DNA复制速度不致于过快,从而减少复制过程中发生错误的几率,维护基因组的稳定性. 相似文献
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Artemis是1个具有多种生物学功能的磷酸化蛋白,它在基因毒性应激引发的细胞周期检测点调控中起重要作用,但其调控机制知之甚少.为了探讨UVC等DNA复制阻滞应激引发的Artemis磷酸化及蛋白表达水平对细胞周期蛋白 E的调控作用和调控机制.首先以Western印迹方法检测Artemis S516-645A突变细胞和Artemis表达降低细胞的细胞周期蛋白E的表达水平,发现ArtemisS516-645A突变细胞和多种Artemis siRNA转染细胞的细胞周期蛋白E表达水平均高于对照细胞.在此基础上,为分析细胞周期蛋白E表达受调控的分子机制,在稳定表达各种磷酸化状态Artemis的HEK-293细胞中导入外源性启动子转录驱动的细胞周期蛋白E表达质粒,发现表达Artemis S516-645A突变体的细胞中外源性的细胞周期蛋白E蛋白表达水平也高于野生型细胞.进一步的研究发现在Artemis蛋白表达降低的细胞中与泛素结合的细胞周期蛋白E减少而蛋白稳定性增加.本研究还发现Artemis蛋白对细胞周期蛋白E的调控过程是不依赖于p53和p21表达的.这些结果表明,Artemis S516-645A突变和Artemis表达降低都可以引起细胞周期蛋白E蛋白水平升高,该调控作用是在转录后水平发生的,可能是干扰了细胞周期蛋白E的泛素化介导的蛋白降解过程,并且该调控作用是独立于p53-p21信号通路的. 相似文献
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Uzbekov RE 《Biochemistry. Biokhimii?a》2004,69(5):485-496
Study of protein expression during the cell cycle requires preparation of pure fractions of cells at various phases of the cell cycle. This was achieved by the development of methods for cell synchronization. Successful cell synchronization requires knowledge of the duration of all phases of the cell cycle. So, in the present review these interrelated problems are considered together. The first part of this review deals with basic methods employed for analysis of duration of cell cycle phases. The second summarizes data on treatments used for cell synchronization. Methods for calculation of percent of cells at various stages of the cell cycle in fractions of synchronized cells are considered in the third part. The fourth part of this review deals with a method of study of protein expression during the cell cycle by means of immunoblotting of synchronized cell fractions. In the Appendix, basic principles are illustrated with practical examples of analysis of the cell cycle, synchronization, and study of expression of some proteins at various stages of the cell cycle using synchronized XL2 (Xenopus laevis) cells. 相似文献
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Fucci (fluorescent ubiquitination-based cell cycle indicator) is able to visualize dynamics of cell cycle progression in live cells; G1- and S-/G2-/M-phase cells expressing Fucci emit red and green fluorescence, respectively. This system could be applied to cell kinetic analysis of tumour cells in the field of cancer therapy; however, it is still unclear how fluorescence kinetics change after various treatments, including exposure to anticancer agents. To explore this, we arrested live HeLa cells expressing the Fucci probes at various cell cycle stages and observed the fluorescence, in conjunction with flow cytometric analysis. X-irradiation, HU (hydroxyurea) and nocodazole arrest cells at G2/M boundary, early S-phase and early M-phase, respectively. Although X-irradiation and HU treatment induced similar accumulation kinetics of green fluorescent cells, nocodazole treatment induced an abnormal red fluorescence at M phase, followed by accumulation of both red and green fluorescent cells with 4N DNA content. We conclude that certain agents that disrupt normal cell cycle regulation could cause unexpected fluorescence kinetics in the Fucci system. 相似文献
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Saran S 《Cell biology international》1999,23(6):399-405
Levels of intracellular calcium, (Ca(2+))(i), from different stages of cell cycle of Dictyostelium discoideum were monitored using the fluorescent Ca(2+)-sensitive dye, Indo 1. Combinations of Ca(2+)-ionophore (A23187) and Ca(2+)-chelator (EGTA) resulted in the inhibition of progression of cell cycle. This delay was caused due to block in G(2)/M-->S phase transition of the cell cycle. Rescue of the cell cycle progression was made with 0.5 m m of exogenous Ca(2+). High (Ca(2+))(i)levels overlapped with the S-phase, of the cell cycle.Results indicate that a high (Ca(2+))(i)level during S-phase is not required for cell cycle progression but for cell-type choice mechanism at the onset of starvation, and these cells tend to follow the prestalk pathway. 相似文献
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To obtain different cell populations at specific cell cycle stages, we used a cell culture synchronization protocol. Effects of five different cell cycle inhibitors acting throughout the cell cycle were examined by DNA flow cytometric analysis of a synchrony/release lymphoma cell line (CEM). The screening synchronized protocol showed that staurosporine, mimosine and aphidicolin are reversible G1 phase inhibitors that act at different times. Staurosporine acted in early G1, exhibited the strongest cytotoxic effect, and induced apoptosis. Mimosine and aphidicolin acted in late G1 and at the G1/S boundary, respectively. Hydroxyurea arrested CEM cells in early S phase, but later than the aphidicolin arrest point. Nocodazole synchronized CEM cells in M phase. All the inhibitors examined in this study can be used to synchronize cells at different phases of the cell cycle and were reversible with little toxicity except for staurosporine which is highly toxic. Because the regulatory mechanism of the cell cycle is disrupted by their effects on protein synthesis, however, these drugs must be used with caution. 相似文献
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来源于天然产物的细胞周期抑制剂 总被引:7,自引:0,他引:7
细胞周期抑制剂可通过选择性地抑制癌细胞的细胞周期周转发挥其抗癌作用,因此通过筛选新的细胞周期抑制活性物质有望寻找到新的抗癌药物。本文按化合物结构类型,简要概述近十年来从天然产物中发现的细胞周期抑制剂的研究概况。 相似文献
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Armiya Sultan Arti Parganiha Tahira Sultan Vivek Choudhary Atanu Kumar Pati 《Biological Rhythm Research》2017,48(3):353-369
Some key elements are common to two fundamental periodic regulatory processes; the circadian cycle and the cell cycle. Underlying mechanisms of coordination between the two processes are critical for proper cellular functioning and physiology. Disruption in the mechanisms of one process may affect the role of other that may direct critical physiological changes and may cause severe diseases like cancer, etc. More or less persuasive evidences evolve from the breast cancer research. In this mini review, we highlighted the molecular coordination’s of the elements of circadian cycle and the cell cycle and their altered expressions associated with the genesis and progression of breast cancer. 相似文献
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Tamar Danon Thomas Christian Takao Igarashi Lydia Cohen Ya‐Ming Hou Lars Juhl Jensen 《Molecular systems biology》2012,8(1)
The cell cycle is a temporal program that regulates DNA synthesis and cell division. When we compared the codon usage of cell cycle‐regulated genes with that of other genes, we discovered that there is a significant preference for non‐optimal codons. Moreover, genes encoding proteins that cycle at the protein level exhibit non‐optimal codon preferences. Remarkably, cell cycle‐regulated genes expressed in different phases display different codon preferences. Here, we show empirically that transfer RNA (tRNA) expression is indeed highest in the G2 phase of the cell cycle, consistent with the non‐optimal codon usage of genes expressed at this time, and lowest toward the end of G1, reflecting the optimal codon usage of G1 genes. Accordingly, protein levels of human glycyl‐, threonyl‐, and glutamyl‐prolyl tRNA synthetases were found to oscillate, peaking in G2/M phase. In light of our findings, we propose that non‐optimal (wobbly) matching codons influence protein synthesis during the cell cycle. We describe a new mathematical model that shows how codon usage can give rise to cell‐cycle regulation. In summary, our data indicate that cells exploit wobbling to generate cell cycle‐dependent dynamics of proteins. 相似文献
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Kun‐Zhi Jia Bo Tang Lu Yu Wei Cheng Rong Zhang Jian‐Fa Zhang Zi‐Chun Hua 《Cell biology international》2010,34(1):49-52
Cellular adenosine accumulates under stress conditions. Few papers on adenosine are concerned with its function in the cell cycle. The cell cycle is the essential mechanism by which all living things reproduce and the target machinery when cells encounter stresses, so it is necessary to examine the relationship between adenosine and the cell cycle. In the present study, adenosine was found to induce G2/M cell‐cycle arrest. Furthermore, adenosine was found to modulate the expression of some important proteins in the cell cycle, such as cyclin B and p21, and to inhibit the transition of metaphase to anaphase in mitosis. 相似文献