SLFN11(Schlafen 11)是一种在进化上高度保守的基因,其表达与多种DNA复制靶向抗癌药物的敏感性密切相关。SLFN11基因编码的蛋白具有RNA酶活性,能够通过切割II型tRNA来抑制蛋白质合成,进而影响细胞对DNA损伤的响应。此外,SLFN11还能够通过...
Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HIV-1...
最新报道显示,人 SLFN11(hSLFN11)可以通过对 tRNA 库的调节实现对蛋白表达 的调控,表现为特异性抑制 HIV-1 结构基因的表达,是新发现的一种 HIV-1 天然 抗病毒因子[5]。为研究马 SLFN11(eSLFN11)与马传染性贫血病毒(Equine infectious anemia virus,EIAV)的相互作用,本实验通过 RT-PCR 从马淋巴细胞 中...
其中之一是结合并隔离tRNA,从而阻止其经过转录后的加工成熟,并且加快了它们的脱酰作用,因此阻止了蛋白质合成。SLFN11不抑制病毒RNA的逆转录、整合、复制和核输出。另外,SLFN11可能在响应外界诱导的DNA损伤的细胞周期停滞和/或诱导凋亡中起作用。因此,在肿瘤细胞中较高水平的SLFN11蛋白有助于预防蛋白质的合成,以及促进...
li等人研究表明slfn11可以通过结合trna,抵消hiv存在所引起的trna的a/u偏好,抑制hiv病毒蛋白的合成,可作为针对hiv的一种新的抗病毒因子。除hiv外,还发现slfn11可抑制其他病毒的复制活性。guo等研究结果显示,除人源slfn11可抑制原型泡沫病毒复制外,牛源和猴源slfn11也可抑制其复制,这种抑制效果是通过病毒和宿主之间不...
其中之一是结合并隔离trna,从而阻止其经过转录后的加工成熟,并且加快了它们的脱酰作用,因此阻止了蛋白质合成。slfn11不抑制病毒rna的逆转录、整合、复制和核输出。另外,slfn11可能在响应外界诱导的dna损伤的细胞周期停滞和/或诱导凋亡中起作用。因此,在肿瘤细胞中较高水平的slfn11蛋白有助于预防蛋白质的合成,以及促进...
Fig. 2: SLFN11 tRNA recognition and nuclease activity. aCryo-EM density map for SLFN11 bound to tRNA with proposed structural model of docked yeast tRNAPhe(PDB code 5AXM).bBottom view of Slfn core domains with highlighted nuclease active sites. Cryo-EM density map for tRNA bound between N...
Here, we present cryo-electron microscopy (cryo-EM) structures of SLFN11 bound to tRNA-Leu and tRNA-Met that give insights into tRNA binding and cleavage, as well as its regulation by phosphorylation at S219 and T230. SLFN11 phosphomimetic mutant S753D adopts a monomeric conformation, shows ...
Instead of targeting single gene product, novel therapies based on the modulation of tRNA-Leu-TAA expression would effect by inhibiting the protein synthesis of a wide spectrum of genes involved in DNA damage response and repair, thus preventing the development of drug resistance by cancer cells....
Our study uncovered a novel mechanism of DNA damage response regulation mediated by SLFN11-dependent tRNA cleavage and codon-specific translational inhibition. The immunomodulation of SLFN11 expression and activation can be a potent novel approach to overcome the wide-spreading resistance of tumor cells...