A translationally regulated Tousled kinase phosphorylates histone H3 and confers radioresistance when overexpressed
A translationally regulated Tousled kinase phosphorylates histone H3 and confers radioresistance when overexpressed
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DOI：
10.1038/sj.onc.1204147
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发表时间：
2001-02-08
期刊：
影响因子：
8
通讯作者：
De Benedetti, A
中科院分区：
文献类型：
--
作者：
Li, Y;DeFatta, R;De Benedetti, A
拟南芥的Tousled基因编码一种蛋白激酶，当突变时，该蛋白激酶会导致花发育异常。从翻译起始因子4 E的过表达诱导上调的mRNA文库中，我们鉴定了哺乳动物Tousled样激酶（TLK 1B）。人TLK 1B mRNA含有一个5 'UTR 1088 nt长，上游有两个AUG密码子，并且被发现对翻译有很强的抑制作用，TLK 1B蛋白几乎只定位于哺乳动物细胞，使它们对电离辐射更具抵抗力。纯化的TLK 1 S在S-10处磷酸化组蛋白H3，在核心组蛋白和分离的染色质中均具有高特异性，表明组蛋白H3是TLK 1B的生理底物。TLK 1B在一种酵母菌株中的表达，该酵母菌株携带主要H3激酶IpI 1的温度敏感性突变，补充了生长缺陷;恢复了组蛋白H3磷酸化的正常水平;并且增加了它们对IR的抗性。H3的磷酸化与促有丝分裂刺激后即刻早期Gems的活化有关，并且与有丝分裂/减数分裂事件期间的染色质凝聚有关，TLK 1B在辐射防护中的可能作用进行了讨论。
The gene Tousled of Arabidopsis Thaliana encodes a protein kinase which, when mutated, results in abnormal flower development, From a library of mRNAs that are translationally upregulated by overexpression of the translation initiation factor 4E, we identified a mammalian Tousled Like kinase (TLK1B), The human TLK1B mRNA contains a 5'UTR 1088-nt-long with two upstream AUG codons, and was found to be very inhibitory for translation, The TLK1B protein localizes almost exclusively mammalian cells rendered them more resistant to ionizing radiation OR). Purified TLK1S phosphorylated histone H3 at S-10 with high specificity both in a mis of core histones and in isolated chromatin, suggesting that histone H3 is a physiological substrate for TLK1B, Moreover, overexpression of TLK1B in transfected cells resulted in a higher degree of H3 phosphorylation. Expression of TLK1B in a yeast strain that harbors a temperature-sensitive mutation of the major H3 kinase, IpI1, complemented the growth defect; restored normal levels of histone H3 phosphorylation; and increased their resistance to IR. Phosphorylation of H3 has been linked to the activation of the immediate-early gems upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events, A possible role for TLK1B in radioprotection is discussed.