美國佛羅里達州立大學醫(yī)學院的研究人員最近解開了一個關于組蛋白的存在一百多年的謎團,。這項發(fā)現(xiàn)或將有助于科學家找到對抗各類疾病(包括癌癥)的治療方法,。該研究報告發(fā)表在Nature Cell Biology雜志上。
一百多年前,，科學家就已經知道,，細胞核內負責DNA包裝(packaging DNA)的組蛋白是一種不易被機體降解的高度穩(wěn)定的蛋白質。但令科學家百思不得其解的是,，如果組蛋白不像其他蛋白質那樣能夠被降解,，那么為什么人類細胞中卻沒有大量組蛋白積累下來。
有人提出這樣的假說：細胞內存在兩個組蛋白庫：一個負責DNA包裝的組蛋白庫很穩(wěn)定,，在某些情況下能在細胞內存在一年以上,，而另一個組蛋白庫起“備份”的作用，即確保細胞內一直有足量的組蛋白可供使用,，因為一旦細胞內組蛋白不足將會引起細胞死亡,。生物醫(yī)藥科學系副教授Akash Gunjan發(fā)現(xiàn)了支持這一假說的證據。
這項發(fā)現(xiàn)揭示了機體在各種復雜情況下都能夠完成對蛋白質的調節(jié)作用,，該研究或許可以使科學家進一步了解到如何通過控制蛋白質的調節(jié)作用來對抗癌細胞以及其他阻斷其他疾病的發(fā)展進程,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
