耶路撒冷希伯來大學(xué)的研究人員發(fā)現(xiàn)了我們體內(nèi)一個(gè)重要分子的另外一個(gè)作用,。該研究促進(jìn)了世界范圍內(nèi)控制疾病的遺傳調(diào)控研究的發(fā)展,，這些疾病包括AIDS和不同類型的癌癥,。
這個(gè)分子就是Lysyl-tRNA合成酶，即LysRS,，是細(xì)胞中最古老的分子之一,。
希伯來大學(xué)的研究人員發(fā)現(xiàn),，LysRS另外一個(gè)重要的角色是作為控制不同基因表達(dá)的中心調(diào)控子,。此外,，在執(zhí)行該功能的時(shí)候，它先前的功能會(huì)終止,。
研究人員介紹說,，這項(xiàng)研究具有重要意義,，因?yàn)長(zhǎng)ysRS與AIDS和癌癥等疾病有關(guān),。艾滋病病毒在復(fù)制過程中會(huì)使用宿主細(xì)胞的LysRS。同樣在一些癌癥中也發(fā)現(xiàn)高水平的LysRS,，比如乳腺癌,。在這些研究背景下，該分子的機(jī)制仍然需要進(jìn)一步挖掘,。
理解LysRS在不同疾病中的調(diào)控影響,，對(duì)全世界范圍內(nèi)的疾病治療研究具有重要貢獻(xiàn)，使得我們可以通過這些療法控制相關(guān)疾病中特定基因的打開或關(guān)閉,。
這項(xiàng)研究結(jié)果發(fā)布在Molecular Cell上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell,12 June 2009 doi:10.1016/j.molcel.2009.05.019
LysRS Serves as a Key Signaling Molecule in the Immune Response by Regulating Gene Expression
Nurit Yannay-Cohen1, 5, Irit Carmi-Levy1, 5, Gillian Kay1, Christopher Maolin Yang2, Jung Min Han3, D. Michael Kemeny2, Sunghoon Kim3, Hovav Nechushtan4, , and Ehud Razin1, ,
1 Department of Biochemistry, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
2 Department of Microbiology and Immunology Program, Life Science Institute, National University of Singapore 117456, Republic of Singapore
3 Center for Medicinal Protein Network and Systems Biology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
4 Oncology Department, Hadassah Hebrew University Medical Center, P.O. Box 12272, Jerusalem 91120, Israel
Lysyl-tRNA synthetase (LysRS) was found to produce diadenosine tetraphosphate (Ap4A) in vitro more than two decades ago. Here, we used LysRS silencing in mast cells in combination with transfected normal and mutated LysRS to demonstrate in vivo the critical role played by LysRS in the production of Ap4A in response to immunological challenge. Upon such challenge, LysRS was phosphorylated on serine 207 in a MAPK-dependent manner, released from the multisynthetase complex, and translocated into the nucleus. We previously demonstrated that LysRS forms a complex with MITF and its repressor Hint-1, which is released from the complex by its binding to Ap4A, enabling MITF to transcribe its target genes. Here, silencing LysRS led to reduced Ap4A production in immunologically activated cells, which resulted in a lower level of MITF inducible genes. Our data demonstrate that specific LysRS serine 207 phosphorylation regulates Ap4A production in immunologically stimulated mast cells, thus implying that LysRS is a key mediator in gene regulation.
