本页上的话题有:
细胞内的染色体(chromosomes)存在着大量的信息。据估计,人体有大约30,000个基因(genes)。每个基因为RNAAlso: ribonucleic acid. RNA is a polymer comprised of the nucleotides A, C, G and U. RNA is the working form of our genetic information. RNA is produced via the process of transcription. Some RNA is used to help build ribosomes (rRNA) and some (mRNA) are used to guide the formation of proteins. Other forms of RNA are used to perform specialized functions in the nucleus.分子指定遗传密码。RNA分子可以被直接利用,也可以用于指导蛋白质(proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins.)的合成,如之前提到的胰岛素(insulinA protein hormone secreted by the pancreas. Insulin controls glucose levels in the body by increasing uptake of glucose into cells of the body. Insulin also stimulates the formation of glycogen and alters fat and protein metabolism.)。细胞内的信息一般是按照预定顺序而流动,即从信息的储存形式(DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. )通过信息的功能形式 (RNA)到最后的产物(蛋白质)。这条通路被所有生物体采用。下面是有关这条通路的图解:
从上图可以看出,DNA被用来合成更多DNA模板。这个过程称为复制(replicationThe process by which DNA is duplicated. DNA replication occurs during the S phase (synthesis) of the cell cycle. Many chemotherapy drugs act during DNA replication. Some are incorporated into the newly replicated DNA and cause problems. Others interfere with enzymes necessary for DNA replication. See topoisomerase.),我们在这里详细介绍。
将DNA(基因)中的某些片段用于合成RNA的过程称为转录(transcriptionThe production of an RNA molecule from a DNA template. An RNA copy of a gene is produced by an enzyme, RNA polymerase. The RNA produced can either be used directly in the cell or can be used to direct the production of a protein through the process of translation. Many of the genes that are altered in cancer cells have potent effects on the process of transcription. See transcription factor.)。我们将较详细地介绍转录过程,因为某些基因在转录过程中的改变在癌症发生上起着重要作用。
如果这些基因在任何时候都处于“启动”状态,则会出现问题。我们生活环境的改变意味着不同基因应在不同时间“启动”。例如,如果我们吃的食物中有大量乳糖(牛奶中的一种糖),那么我们机体对之作出的反应是,“启动”(转录)基因,导致分解乳糖的酶(enzymes)的产生。如果是不同的糖或营养素,应该“启动”相应的基因以对付不同的物质。
转录
转录(transcription)是为了制作基因(geneA stretch of DNA that leads to the production of an RNA. The RNA is produced during the process of transcription. This RNA can be used to guide the formation of a protein via translation or can be used directly in the cell.)的RNA复制本。这种RNA能指导蛋白质(protein)合成或在细胞内直接被利用。含有细胞核(nucleusPlural, nuclei. A subcellular organelle that contains the chromosomes. Present in eukaryotic cells, the nucleus is surrounded by the nuclear envelope. Within the nucleus is a region called the nucleolus in which the parts of ribosomes are constructed. The nuclear pores allow for the import and export of materials.)的所有细胞都存在着完全一样的遗传信息。之前曾提到过,在某种细胞中,只有很少基因会在任何时间被用于RNA合成。在正常细胞里,转录过程会受到以下的严格管理:
- 基因必须在规定时间被转录。
- 从基因制得的RNA的量必须正确。
- 只有需要的基因才能被转录。
- “关闭”转录与“打开”转录一样重要。
你可以把以上管理比作为对一条精心设计的流水作业线的管理,如同你在工厂里所看到的那样。需要生产时,“打开” 流水作业线;不需要生产时,“关闭” 流水作业线。
人类染色体(chromosomes)储存着大量信息。每个染色体有一条长长的DNA链,这条链由几百万个核苷酸(nucleotides)组成。一个基因只占据染色体的一个小小的片段。
以下动画中显示的是DNA在染色体中如何组织排列的。DNA紧紧地缠绕和螺旋化以减少所占的空间,就像在线轴上绕线一样。下面展示的染色体已经被复制了并且呈现标志性的X状。细胞分裂前的染色体就是呈现这种状态。
转录的步骤
为了转录(transcription)成功,必须用一种方法确定转录的“起、止”时间。这个“起、止”时间由某些特别蛋白质(proteins)控制。这些蛋白质与即将被转录的基因的起始点结合。我们把这些蛋白质叫做转录因子(transcription factors)。
转录过程分为以下几个步骤:
- 转录因子识别被转录基因的启动部位(启动子)。
- 合成RNA的酶(enzymeA protein that speeds up the process of chemical reactions in the body without becoming altered in the process. Almost every biological process is driven by the activity of enzymes. Without enzyme catalysts, the complex reactions that build and break down cell parts would not happen at a rate compatible with life. Enzyme names usually describe the reaction that is being catalyzed and all of them end in -ase.)(RNA聚合酶)与转录因子结合并识别启动部位。
- RNA聚合酶顺着DNA方向制作复制本,一直到该基因末端。
- RNA聚合酶脱落,RNA被释放。这样的复制过程会重复许多遍。
- 如果复制出的RNA含有蛋白质编码,则该RNA会离开细胞核(nucleus)而进入细胞溶质。
注意,上面提到的那个基因实际上是DNA分子(染色体)上的一段核苷酸。
转录因子的功能异常几乎在所有已知的癌症中都能见到。既然转录因子对细胞正常活动时如此必要,其异常功能会对该细胞所有其他部分产生及其严重的影响。再用工厂的流水作业线作为比喻,功能异常的转录因子会使本该停止的流水作业线仍然不停地运行,生产出过多的产品。而在需要它运行时,却不运行,结果导致某些产品缺乏。
转录因子
下面例子显示了人类癌症中功能异常的转录因子:
- p53A tumor suppressor gene that is mutated in over 50% of cancers of all types. The p53 protein is a transcription factor that controls entry into the cell division cycle. Many signals about the health of a cell are relayed to the p53 protein. This results in a decision by the cell as to whether or not cell division should occur. If the cell is damaged and can not be repaired, the p53 protein is involved in triggering a chain of events that causes the cell to kill itself in a process termed apoptosis. Cells defective for p53 do not have these controls and tend to divide even when conditions are not favorable. Like all tumor suppressors, the p53 gene is normally involved in slowing or monitoring cell division. (TP53)- 控制p53转录因子(蛋白质)生成的基因在一半多的癌症中变异。p53基因生成的蛋白质很重要,因为它控制了参与细胞分裂的基因的转录。更多关于p53基因的信息在癌症抑制基因一章中。
- RbA tumor suppressor. The Rb gene is mutated in many different cancers but was initially described due to its role in the development of an eye cancer, retinoblastoma, which usually strikes young children. The protein product of the gene is a transcription factor that controls the expression of genes important in driving cells into the division process. - 这个基因的蛋白质产物是一个拥有有趣功能的转录因子。实际上,它的功能是阻碍其他的转录因子。这样,Rb防止了细胞分裂过程所需主要基因的转录。最初,Rb被描述为在眼癌(retinoblastomaA cancer of the retina. Found most often in small children; this disease has been linked to the inheritance of mutated copies of the Rb tumor suppressor gene. For more information, see the entries on Rb and Tumor Suppressor.)中存在的基因变异,它的名字也由此得来。现在,我们得知Rb蛋白质在很多不同的癌症中起作用。更多关于Rb 基因的信息在癌症抑制基因一章中。
- 雌激素受体 (ERThe endoplasmic reticulum. A large subcellular network of membranes within the cell. The ER membrane, an extension of the outer nuclear membrane, has two structurally and functionally distinct regions: Rough ER (RER) and Smooth ER (SER). The RER ( the portion closer to the nucleus) has a 'rough' appearance due to ribosomes attached to the surface of the membrane. Ribosomes attached to the ER are producing proteins that are to be released from the cell. Smooth ER (SER) appears smooth and is devoid of ribosomes. SER functions include the detoxification of drugs, the production of steroid hormones and the formation of membrane components. Molecules produced by the RER and SER can be packaged into vesicles and sent to other locations in the cell or to the outside of the cell.) - 这个蛋白质和进入细胞的雌激素结合。雌激素是由卵巢分泌的类固醇(酯类)激素。蛋白质和激素的结合体成为转录分子,使目标细胞分裂。 这个受体在女性生殖器官(例如乳房,卵巢)中是激活的。正因如此,雌激素被认为是一个刺激癌症在这些部位生成的因素。
雌激素的作用机制显示如下:
绿色小球代表雌激素。 雌激素是具有疏水性(hydrophobicDescribes molecules which do not interact with water or other polar molecules. The lipid hormones and fat are examples of hydrophobic molecules. From hydro, water and phobos, fearing)的小分子物质,它通过脂膜进入细胞。一旦进入细胞,雌激素便能与其受体 (橙色所示) 结合。所形成的复合体再与细胞核(nucleus)内的DNA结合,使基因得到转录。
现已研制出几种药物,试图阻断雌激素对基因的“启动”作用。临床上常用的他莫昔芬(tamoxifen)属于这类药物,它能部分地抑制雌激素活性。他莫昔芬在下面的动画中用粉色表示。
这类药物应该会减慢那些对雌激素及其受体敏感的肿瘤的生长速度。有关雌激素及其受体的更多信息,参看“癌症治疗”一章。
转录因子对细胞分裂的重要性已经反复强调过了。恶性肿瘤是因为细胞分裂得不到控制而引起的。所以,我们要讨论的下一个过程就是细胞分裂。了解正常的细胞分裂过程十分重要,这样会有利于我们理解细胞分裂中出现的问题。
翻译
信使RNA (mRNAMessenger RNA, an RNA molecule is a copy of a particular gene that is used in the production of a protein. Messenger RNA is produced in the nucleus via the process of transcription and is exported through holes or pores in the nuclear envelope into the cytoplasm. mRNA then attaches to a ribosome where the encoded message is read to produce a protein in the process termed translation.)在通过上述转录(transcription)过程而生成后,被在细胞核(nucleus)里进行加工,然后被释放到细胞液(cytosolThe semi-liquid portion of the cell outside the nucleus, excluding the organelles. Compare to cytoplasm.)中。
之后,mRNA 被细胞液中的核糖体(ribosomeThe organelle that is responsible for the production of protein. Ribosomes are comprised of two subunits that are synthesized in the nucleus at the nucleolus. Ribosomes bind to mRNA and use the information encoded in the RNA to synthesize a protein. Since the mRNA is copied from the gene in the DNA, it is really the DNA that encodes the information.)亚单位识别,由核糖体对其信息进行“解读”来合成蛋白质(protein)。指导蛋白质合成的信息被编码在组成mRNA 的核苷酸 (nucleotides)序列里。三个核苷酸为一组(称为密码子codons)被核糖体“解读”,使某个氨基酸(amino acidA monomer building block used to build proteins. There are many amino acids but only about twenty different kinds are found in most proteins.)插入正在合成的多肽(蛋白质)中。下面的动画显示了该过程。
蛋白质合成后,获得具有活性的折叠结构,便能执行它在细胞内的功能。蛋白质的正确折叠、运输、功能发挥、以及最终破坏,都受着严格的控制和管理。
控制上述过程的基因(genes)常在癌症中遭到损害,而且出现功能异常。
更多有关本章的信息可以在Robert A. Weinberg所著的《癌症生物学》(The Biology of Cancer)一书第一章中被找到.
基因功能总结
中心法则
- 我们染色体中的DNA包含了基因信息,这些基因信息转录成为RNA。
- 有很多不同种类的RNA (tRNA, mRNA, rRNA等等)。它们由相同的成分组成,但拥有不同的功能,位置,和结构。
- 信使RNA (mRNA)可以被翻译成蛋白质。标准的信息流程为:
- DNA→RNA→蛋白质
- 一系列总是“启动”的基因是很危险的。不同的基因需要在不同的时间,根据特定细胞的需求和功能而被“启动”。
转录
- 转录的目的是形成基因的RNA复制本。
- 转录因子通过与基因起始点结合来确定转录开始的位置。
- p53, Rb, 和雌激素受体都是转录因子,它们在癌症中出现功能障碍。
- 转录过程可以分为以下几个步骤:
- 转录因子识别被转录基因的启动部位(启动子)。
- 合成RNA的酶(RNA聚合酶)与转录因子结合。
- RNA聚合酶顺着DNA方向制作复制本。
- RNA聚合酶脱落,RNA被释放。
- RNA留在细胞和内或离开细胞核而进入细胞溶质。
翻译
- 翻译的目的是利用mRNA所带的编码信息合成蛋白质。
- 翻译过程可以分为以下几个步骤:
- mRNA离开细胞核,并在细胞溶脂中被核糖体亚基识别和结合。
- 核糖体一次“解读”三个核苷酸(一个密码子)。
- 核糖体根据密码子插入氨基酸到不断增长的蛋白链。
- 当核糖体遇到终止密码子时蛋白质合成停止。
- 蛋白质进入一个受严格控制的折叠过程,并且获得一个完全折叠的结构。
- 控制蛋白质的正确折叠,运输,活动,和最终破坏的基因在癌症中常常遭到损害,或出现功能异常。