美国佛罗里达州立大学医学院的研究人员最近解开了一个关于组蛋白的存在一百多年的谜团。这项发现或将有助于科学家找到对抗各类疾病(包括癌症)的治疗方法。该研究报告发表在Nature Cell Biology杂志上。
一百多年前，科学家就已经知道，细胞核内负责DNA包装(packaging DNA)的组蛋白是一种不易被机体降解的高度稳定的蛋白质。但令科学家百思不得其解的是，如果组蛋白不像其他蛋白质那样能够被降解，那么为什么人类细胞中却没有大量组蛋白积累下来。
有人提出这样的假说：细胞内存在两个组蛋白库：一个负责DNA包装的组蛋白库很稳定，在某些情况下能在细胞内存在一年以上，而另一个组蛋白库起“备份”的作用，即确保细胞内一直有足量的组蛋白可供使用，因为一旦细胞内组蛋白不足将会引起细胞死亡。生物医药科学系副教授Akash Gunjan发现了支持这一假说的证据。
这项发现揭示了机体在各种复杂情况下都能够完成对蛋白质的调节作用，该研究或许可以使科学家进一步了解到如何通过控制蛋白质的调节作用来对抗癌细胞以及其他阻断其他疾病的发展进程。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Cell Biology 11, 925 - 933 (2009) 5 July 2009 | doi:10.1038/ncb1903
Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis
Rakesh Kumar Singh1, Marie-Helene Miquel Kabbaj1, Johanna Paik1 & Akash Gunjan1
Histone levels are tightly regulated to prevent harmful effects such as genomic instability and hypersensitivity to DNA-damaging agents due to the accumulation of these highly basic proteins when DNA replication slows down or stops. Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae. Here we demonstrate that excess histones associate with Rad53 in vivo and seem to undergo modifications such as tyrosine phosphorylation and polyubiquitylation, before their proteolysis by the proteasome. We have identified the Tyr 99 residue of histone H3 as being critical for the efficient ubiquitylation and degradation of this histone. We have also identified the ubiquitin conjugating enzymes (E2) Ubc4 and Ubc5, as well as the ubiquitin ligase (E3) Tom1 (temperature dependent organization in mitotic nucleus 1), as enzymes involved in the ubiquitylation of excess histones. Regulated histone proteolysis has major implications for the maintenance of epigenetic marks on chromatin, genomic stability and the packaging of sperm DNA.
1 Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306–4300, USA.
