文章来源:未知 文章作者:meng 发布时间:2010-02-08 01:03 字体: [ ]  进入论坛

Using an elaborate(精心制作的) sleuthing(侦查) system they developed to probe how cells manage their own division, Johns Hopkins scientists have discovered that common but hard-to-see sugar switches are partly in control. Because these previously1 unrecognized sugar switches are so abundant(充裕的,丰富的) and potential targets of manipulation(操作,处理) by drugs, the discovery of their role has implications for new treatments for a number of diseases, including cancer, the scientists say.

In the January 12 edition of Science Signaling, the team reported that it focused efforts on the apparatus2(装置,设备) that enables a human cell to split into two, a complicated biochemical(生物化学的) machine involving hundreds of proteins. Conventional wisdom was that the job of turning these proteins on and off — thus determining if, how and when a cell divides — fell to phosphates(磷酸盐) , chemical compounds containing the element phosphorus(磷) , which fasten to and unfasten from proteins in a process called phosphorylation(磷脂化作用) .

Instead, the Johns Hopkins scientists say, there is another layer of regulation by a process of sugar-based protein modification3 called O-GlcNAcylation (pronounced O-glick-NAC-alation). "This sugar-based system seems as influential4 and ubiquitous(普遍存在的) a cell-division signaling pathway as its phosphate counterpart and, indeed, even plays a role in regulating phosphorylation itself," says Chad Slawson, Ph.D., an author of the paper and research associate in the Department of Biological Chemistry, Johns Hopkins University School of Medicine.

Because the sugar molecule5 has some novel qualities — it is small, easily altered, and without an electrical charge — it is virtually imperceptible(感觉不到的,极细微的) to researchers using standard physical techniques of detection such as mass spectrometry(质谱分析法) .

Suspecting that the sugar known as O-GlcNAc might play a role in cell division, the Hopkins team devised a protein-mapping scheme using new mass spectrometric methods. Essentially6, they applied7 a combination of chemical modification and enrichment methods, and new fragmentation(破碎,分裂) technology to proteins that comprise the cell division machinery8 in order to figure out and analyze9 their molecular10 makeup11, identifying more than 150 sites where the sugar molecule known as O-GlcNAc was attached. Phosphates were found to be attached at more than 300 sites.

They noticed that when an O-GlcNAc molecule was located near a phosphate site, or at the same site, it prevented the phosphate from attaching. The proteins involved in cell division weren't phosphorylated and activated12 until O-GlcNAc detached.

"I think of phosphorylation as a micro-switch that regulates the circuitry(电路系统) of cell division, and O-GlcNAcylation as the safety switch that regulates the microswitches," says Gerald Hart, Ph.D., the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine.

Using a standard human cell line (HeLa cells), the scientists discovered abnormalities when they disrupted the cell division process by adding extra O-GlcNAc. Although the cell's chromosome-containing nuclei13(核心) divided normally, the cells themselves didn't divide, resulting in too many nuclei per cell — a condition known as polyploidy(多倍体) that's exhibited by many cancer cells.

The researchers not only mapped O-GlcNAc and phosphorylation sites but also measured changes in the cell division machinery, because, Hart says, the chemical changes act more like "dimmer(调光器) " switches, than simple on/off ones.

As important as the discovery is to a deeper understanding of cell division, Hart says, this extensive cross talk between O-GlcNAc and phosphorylation is paradigm-shifting in terms of signaling. Signaling is how a cell perceives its environment, and how it regulates its machinery in response to stimuli14(刺激,促进因素) . The new sugar switches reveal that the cellular15 circuitry is much more complex than previously thought, he adds.


1 previously bkzzzC     
  • The bicycle tyre blew out at a previously damaged point.自行车胎在以前损坏过的地方又爆开了。
  • Let me digress for a moment and explain what had happened previously.让我岔开一会儿,解释原先发生了什么。
2 apparatus ivTzx     
  • The school's audio apparatus includes films and records.学校的视听设备包括放映机和录音机。
  • They had a very refined apparatus.他们有一套非常精良的设备。
3 modification tEZxm     
  • The law,in its present form,is unjust;it needs modification.现行的法律是不公正的,它需要修改。
  • The design requires considerable modification.这个设计需要作大的修改。
4 influential l7oxK     
  • He always tries to get in with the most influential people.他总是试图巴结最有影响的人物。
  • He is a very influential man in the government.他在政府中是个很有影响的人物。
5 molecule Y6Tzn     
  • A molecule of water is made up of two atoms of hygrogen and one atom of oxygen.一个水分子是由P妈?f婘??妈?成的。
  • This gives us the structural formula of the molecule.这种方式给出了分子的结构式。
6 essentially nntxw     
  • Really great men are essentially modest.真正的伟人大都很谦虚。
  • She is an essentially selfish person.她本质上是个自私自利的人。
7 applied Tz2zXA     
  • She plans to take a course in applied linguistics.她打算学习应用语言学课程。
  • This cream is best applied to the face at night.这种乳霜最好晚上擦脸用。
8 machinery CAdxb     
  • Has the machinery been put up ready for the broadcast?广播器材安装完毕了吗?
  • Machinery ought to be well maintained all the time.机器应该随时注意维护。
9 analyze RwUzm     
vt.分析,解析 (=analyse)
  • We should analyze the cause and effect of this event.我们应该分析这场事变的因果。
  • The teacher tried to analyze the cause of our failure.老师设法分析我们失败的原因。
10 molecular mE9xh     
  • The research will provide direct insight into molecular mechanisms.这项研究将使人能够直接地了解分子的机理。
  • For the pressure to become zero, molecular bombardment must cease.当压强趋近于零时,分子的碰撞就停止了。
11 makeup 4AXxO     
  • Those who failed the exam take a makeup exam.这次考试不及格的人必须参加补考。
  • Do you think her beauty could makeup for her stupidity?你认为她的美丽能弥补她的愚蠢吗?
12 activated c3905c37f4127686d512a7665206852e     
adj. 激活的 动词activate的过去式和过去分词
  • The canister is filled with activated charcoal.蒸气回收罐中充满了活性炭。
13 nuclei tHCxF     
  • To free electrons, something has to make them whirl fast enough to break away from their nuclei. 为了释放电子,必须使电子高速旋转而足以摆脱原子核的束缚。
  • Energy is released by the fission of atomic nuclei. 能量是由原子核分裂释放出来的。
14 stimuli luBwM     
  • It is necessary to curtail or alter normally coexisting stimuli.必需消除或改变正常时并存的刺激。
  • My sweat glands also respond to emotional stimuli.我的汗腺对情绪刺激也能产生反应。
15 cellular aU1yo     
  • She has a cellular telephone in her car.她的汽车里有一部无线通讯电话机。
  • Many people use cellular materials as sensitive elements in hygrometers.很多人用蜂窝状的材料作为测量温度的传感元件。
TAG标签: sugar cells division