SCF和APC/C的结构及功能

细胞周期蛋白依赖性蛋白激酶(cyclin dependent kinases,CDKs)是细胞周期进行的推动力,泛素-蛋白酶体途径(ubiquitin-proteasome pathway,UPP)通过对细胞周期蛋白(cyclin)和CDK抑制物(CDK inhibitors,CKIs)的蛋白质水解作用来实现对CDKs活性的调控。SCF(Skp1-Cul1-F-box protein)和APC/C(anaphase-promoting complex/cyclosome)这两个泛素连接酶复合物参与了很多细胞周期调节因子的泛素化作用。它们参与的蛋白质降解系统的功能失调可能导致细胞增殖紊乱、基因组不稳定和肿瘤的发生。现对这两个泛素连接酶复合物的结构以及它们在细胞周期调控和肿瘤发生机制中的作用进行综述。     

ATM、ATR和DNA损伤介导的细胞周期阻滞

ATM和ATR属于PIKK家族,是DNA损伤检查点的主要成员。它们被不同类型的DNA损伤所激活,通过磷酸化相应的下游蛋白Chk1和Chk2等,调节细胞周期各个检查点,引起细胞周期阻滞,使DNA损伤得以修复。ATM和ATR在维持基因组的稳定性中起到至关重要的作用。本文着重综述有关ATM和ATR在DNA损伤介导的细胞周期阻滞中发挥的作用以及相互关系的最新研究进展。     

Bora在细胞功能调控中的作用和机制研究进展

Aurora蛋白激酶A及Polo样蛋白激酶1（PLK在）作为重要的细胞周期调节蛋白可参与调控纺锤体组装、有丝分裂等细胞进程,但其激活机制及在有丝分裂中的作用机制仍然不是很清楚。Bora作为Aurora蛋白激酶A的结合蛋白,在果蝇和脊椎动物中功能高度保守,其主要通过结合Aurora蛋白激酶A从而调节Aurora蛋白激酶A的活性、促进PLK1的磷酸化、调节纺锤体的组装以及调控细胞周期进程等。随着对Bora研究的深入,人们对AuroraA和PLK1的激活机制以及Bora、Aurora蛋白激酶A、PLK1三者对细胞的调控也有了进一步的认识。主要综述Bora在细胞功能调控中的作用和研究机制。     

高等植物细胞周期调控研究进展

高等植物的细胞周期（cell cycle)在其生长发育过程中受严格调控的,细胞周期的运转是基因有序表达的结果,并受的因素的影响,植物细胞周期研究近年来已取得的较大的进展,本文综述了近几年与植物细胞周期调控相关的细胞周期蛋白（cyclins),细胞周期蛋白依赖性激酶（CDKs)等内部调控因子及外源影响因素的研究进展。     

Cyclin D1与细胞周期调控

细胞周期是细胞生命活动中一个最重要的过程,其关键是G1 期的启动.细胞周期蛋白(Cyclin)、细胞周期蛋白依赖性激酶(CDKs)和CDK抑制因子(CKIs)是参与钿胞周期调控的主要因子.Cyclin D1是调控细胞周期G1期的关键蛋白,是一个比其他Cyclins更加敏感的指标,对细胞周期调控至关重要.综述Cyclin D1的结构和功能及其在肿瘤组织中的表达特征,初步分析Cyclin D在昆虫细胞周期调控的研究.     

植物细胞周期调控因子及其功能的研究进展

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。     

细胞周期检查点的分子机制

细胞在长期的进化过程中发展出了一套保证细胞周期中ＤＮＡ复制和染色体分配质量的检查机制,通常被称为细胞周期检查点（ｃｈｅｃｋｐｏｉｎｔ）。当细胞周期进程中出现异常事件,这类调节机制就被激活,及时地中断细胞周期的运行,待细胞修复或排除了故障后,细胞周期才能恢复运转。根据“质量控制”的内容,可将细胞周期检查点分为三种。第一种负责查看ＤＮＡ有无损伤,称为ＤＮＡ损伤检查点;第二种负责ＤＮＡ复制的进度,称为ＤＮＡ复制检查点;第三类是管理染色体的正确分配与否,称为纺锤体组装检查点。本文围绕检查点工作的这三个方面对其分子机制作一个简单的论述。     

Rho小G蛋白相关激酶的结构与功能

Rho小G蛋白家族是Ras超家族成员之一,人类Rho小G蛋白包括20个成员,研究最清楚的有RhoA、Rac1和Cdc42。Rho小G蛋白参与了诸如细胞骨架调节、细胞移动、细胞增殖、细胞周期调控等重要的生物学过程。在这些生物学过程的调节中,Rho小G蛋白的下游效应蛋白质如蛋白激酶（p21-activated kinase,PAK）、ROCK（Rho-kinase）、PKN（protein kinase novel）和MRCK（myotonin-related Cdc42-binding kinase）发挥了不可或缺的作用。迄今研究发现,PAK可调节细胞骨架动力学和细胞运动,另外,PAK通过MAPK（mitogen-activated protein kinases）参与转录、细胞凋亡和幸存通路及细胞周期进程;ROCK与肌动蛋白应力纤维介导黏附复合物的形成及与细胞周期进程的调节有关;哺乳动物的PKN与RhoA/B/C相互作用介导细胞骨架调节;MRCK与细胞骨架重排、细胞核转动、微管组织中心再定位、细胞移动和癌细胞侵袭等有关。该文简要介绍Rho小G蛋白下游激酶PAK、ROCK、PKN和MRCK的结构及其在细胞骨架调节中的功能,重点总结它们在真核细胞周期调控中的作用,尤其是在癌细胞周期进程中所发挥的作用,为寻找癌症治疗的新靶点提供理论依据。     

人乳头瘤病毒E7蛋白对细胞周期G1/S检查点的影响

高危型人乳头瘤病毒(HPV)感染与宫颈癌的发生关系已经明确,HPV编码的早期蛋白E7是HPV致宫颈癌的主要相关蛋白之一。G_1/S检查点是细胞周期中不可逆的关键点,决定了细胞进入细胞周期与否,与肿瘤的发生发展关系密切。pRb蛋白是调控细胞周期G_1/S检查点中的限速底物,是起调控作用的主要因子之一。E7通过影响pRb蛋白、E2F家族、Cyclin/CDK2复合物、p27蛋白、Dyrk1B等细胞周期相关蛋白来影响G_1/S检查点的正常工作,形成失控的细胞增殖。高危型HPV E7蛋白对细胞周期检查点的影响,既是HPV致癌机制的重要组成部分,也可能成为攻克此类癌症的突破口。本文综述了高危型HPV E7蛋白对细胞周期G_1/S检查点的影响。     

蛋白激酶C与细胞周期

近年的研究表明,PKC涉及到细胞的周期调节。在酵母细胞和哺乳动物细胞均发现PKC参与细胞周期调控,从而提示PKC可能在进化上是一种保守的细胞周期调节子。一般认为PKC在两个点上对细胞周期起作用,即G1期和G2期到M期的过渡期（G2／M）。在G1期,PKC分别在早G1期和晚G1期作用有所不同,主要作用表现在使细胞停留在G1期的中末阶段,这一过程,主要涉及到抑制肿瘤抑制因子－成视网膜细胞瘤（Rb)蛋白的磷酸化。PKC的主要作用是降低周期素依赖激酶CDK2的活性、降低周期素E和A的表达和增加周期素依赖的周期抑制蛋白p21^WAF1和p27^KIP1的表达;在G2／M期,PKC对细胞周期的调节主要与Cdc2(CDK1)的活性抑制有关。     

Regulation of Cell Division in Arabidopsis

The study of cell cycle control in plants is expected to contribute to the understanding of plants' unique developmental features. The principal regulators of the eukaryotic cell cycle, namely, cyclin-dependent kinases (CDKs) and cyclins, are also conserved in plants. This review is concerned with our present knowledge on cell cycle regulation in Arabidopsis thaliana, which is widely accepted as a model plant for the study of a broad range of biological questions. Up to the present, 2 CDKs and 11 cyclins have been identified in Arabidopsis. While the expression of one of these CDKs has been found to be positively correlated with the competence of cells to divide, cyc1A1 expression of the cyclin has been almost exclusively confined to dividing cells. Although much remains to be studied concerning upstream regulators of these genes, the successful introduction of mutant CDKs into plants demonstrates the potential of using such an approach to intentionally modulate the plant cell cycle and development.     

Redundancy or specificity? The role of the CDK Pho85 in cell cycle control

It is generally accepted that progression through the eukaryotic cell cycle is driven by cyclin-dependent kinases (CDKs), which are regulated by interaction with oscillatory expressed proteins called cyclins. CDKs may be separated into 2 categories: essential and non-essential. Understandably, more attention has been focused on essential CDKs because they are shown to control cell cycle progression to a greater degree. After clearly determining the basic and “core” mechanisms of essential CDKs, several questions arise. What role do non-essential CDKs play? Are these CDKs functionally redundant and do they serve as a mere backup? Or might they be responsible for some accessory tasks in cell cycle progression or control? In the present review we will try to answer these questions based on recent findings on the involvement of non-essential CDKs in cell cycle progression. We will analyse the most recent information with regard to these questions in the yeast Saccharomyces cerevisiae, a well-established eukaryotic model, and in its unique non-essential CDK involved in the cell cycle, Pho85. We will also briefly extend our discussion to higher eukaryotic systems.     

CKS1At overexpression in Arabidopsis thaliana inhibits growth by reducing meristem size and inhibiting cell-cycle progression

The SUC1/CKS1 proteins associate with cyclin-dependent kinases (CDKs) and play an essential role in the regulation of the cell cycle. Recently, an Arabidopsis thaliana SUC1/CKS1 homologous gene, designated CKS1At, has been cloned. Here, overexpression of CKS1At in Arabidopsis is shown to reduce leaf size and root growth rates. Reduced root growth resulted primarily from an increase of the cell-cycle duration and a shortening of the meristem. Endoreduplication was unaffected. The increased cell-cycle duration was associated with an equal extension of both the G1 and G2 phases. This inhibition was due to the binding of CDK subunits with CDKs. The reduced growth rates in response to altered cell-cycle gene expression demonstrates a direct dependence of plant growth rates on cell-cycle regulation.     

A Novel Member of the Cyclin-Dependent Kinase Family in Paramecium tetraurelia

Passage through the cell cycle in eukaryotes requires the successive activation of different cyclin-dependent protein kinases. Here, we describe the identification and characterization of a novel class of cyclin-dependent protein kinase, termed Cdk2, in the ciliate Paramecium tetraurelia. It is 301 amino acids long, 7 amino acids shorter than Cdk1, the CDK that is associated with macronuclear DNA synthesis. All the catalytic domains typical of protein kinases can be located within the sequence and putative regulatory phosphorylation sites equivalent to Thr14, Tyr15, and Thr161 in human CDK1 are also conserved. The 'PSTAIRE' region characteristic of most CDKs is perfectly conserved. Cdk2 shares only 48% homology to Cdk1 at the amino acid level, suggesting that the evolutionary separation of Cdk1 and Cdk2 is ancient, and implying that they have different roles in cell cycle regulation. Like Cdk1, Cdk2 does not bind to yeast p13suc1, even though it has better conservation of p13suc1 binding sites than Cdk1 does. The Cdk2 protein level is relatively constant throughout the vegetative cell cycle. Cdk2 exhibits kinase activity towards bovine histone H1 in vitro with the maximal level late in the cell cycle, suggesting it may be involved in the regulation of cytokinesis. Our results further support the view that an analogue of the cyclin-dependent kinase cell cycle regulatory system like that of yeast and higher eukaryotic cells operates in Paramecium and that a family of cyclin-dependent kinases may control different aspects of the Paramecium cell cycle.     

Chemical inhibitors of cyclin-dependent kinases

Transient activation o f cyclin-dependent kinases (CDKs) is responsible for transition through the successive phases of the cell-division cycle. Major changes in the expression and regulation of CDKs have been described in human tumours. Enzymatic screening is starting to uncover chemical inhibitors o f CDKs that arrest the cell cycle at various steps. This review summarizes our knowledge of the first generation inhibitors, their molecular mechanisms of action and their effects on the cell cycle and apoptosis, and discusses their potential as synchronizing agents, as ligands for affinity chromatography and as therapeutic agents.     

The retinoblastoma pathway in plant cell cycle and development

The activity of cyclin-dependent kinases (CDKs) on specific targets mediates the temporal regulation of plant cell cycle transitions. The sequential activity of CDKs and the spatial regulation of cell proliferation during plant development, however, are still poorly understood. Understanding these aspects depends on the identification of the downstream targets and upstream modulators of CDKs and their regulation in response to mitogenic and/or differentiation signals. Current efforts to elucidate the answers to these questions are very promising; in particular, recent works reveal the essential role that the retinoblastoma pathway plays in controlling cell cycle progression and, presumably, some developmental events.