Inhibition of the Deubiquitinase Usp14 Diminishes Direct MHC Class I Antigen Presentation.
Inhibition of the Deubiquitinase Usp14 Diminishes Direct MHC Class I Antigen Presentation.
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去泛素酶USP14的抑制减少了直接的MHC I类抗原表现。
DOI：
10.4049/jimmunol.1700273
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发表时间：
2018-02-01
期刊：
影响因子：
--
通讯作者：
Dolan BP
中科院分区：
文献类型：
--
作者：
Palmer AL;de Jong A;Leestemaker Y;Geurink PP;Wijdeven RH;Ovaa H;Dolan BP
感染或转化的细胞必须在MHC I类分子上呈递来自内源性蛋白质的肽，以便被抗原特异性细胞毒性T细胞识别和消除。在肽生成的第一步，蛋白质被蛋白酶体降解。在这里，我们研究了泛素特异性蛋白酶14 （Usp14）的作用，这是一种蛋白酶体相关的去泛素酶，使用配体稳定的模型蛋白作为自身抗原表达，直接递呈抗原。Usp14的化学抑制减少了模型抗原肽的直接呈递，当呈递仅限于蛋白质的缺陷核糖体产物（或DRiP）形式时，效果尤其明显。此外，通过表达无催化活性的Usp14，可以减少来自DRiP抗原的特异性呈递。Usp14的抑制作用并没有明显改变蛋白质的合成，只是部分延迟了蛋白质的降解，这是通过诱导模型蛋白降解时半衰期的轻微增加来测量的。综上所述，这些数据表明功能性Usp14增强了直接抗原呈递，尤其是drip衍生肽，这表明drip的加工在某些方面不同于其他形式的抗原。
Infected or transformed cells must present peptides derived from endogenous proteins on MHC class I molecules in order to be recognized and targeted for elimination by antigen-specific cytotoxic T cells. In the first step of peptide generation, proteins are degraded by the proteasome. Here, we investigated the role of the ubiquitin-specific protease 14 (Usp14), a proteasome-associated deubiquitinase, in direct antigen presentation using a ligand-stabilized model protein expressed as a self-antigen. Chemical inhibition of Usp14 diminished direct presentation of the model antigenic peptide, and the effect was especially pronounced when presentation was restricted to the Defective Ribosomal Product (or DRiP) form of the protein. Additionally, presentation specifically from DRiP antigens was diminished by expression of a catalytically inactive form of Usp14. Usp14 inhibition did not appreciably alter protein synthesis and only partially delayed protein degradation as measured by a slight increase in the half-life of the model protein when its degradation was induced. Taken together, these data indicate that functional Usp14 enhances direct antigen presentation, preferentially of DRiP-derived peptides, suggesting that the processing of DRiPs is in some ways different from other forms of antigen.
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影响因子：
3.2
作者：
de Jong, Annemieke;Merkx, Remco;Berlin, Ilana;Rodenko, Boris;Wijdeven, Ruud H. M.;El Atmioui, Dris;Yalcin, Zeliha;Robson, Craig N.;Neefjes, Jacques J.;Ovaa, Huib
通讯作者：
Ovaa, Huib
影响因子：
6.7
作者：
Croft NP;Smith SA;Wong YC;Tan CT;Dudek NL;Flesch IE;Lin LC;Tscharke DC;Purcell AW
通讯作者：
Purcell AW
DOI：
10.1523/jneurosci.2635-09.2009
发表时间：
2009-09-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen PC;Qin LN;Li XM;Walters BJ;Wilson JA;Mei L;Wilson SM
通讯作者：
Wilson SM
影响因子：
8
作者：
Dolan, Brian P.;Bennink, Jack R.;Yewdell, Jonathan W.
通讯作者：
Yewdell, Jonathan W.
影响因子：
3.7
作者：
Palmer AL;Dolan BP
通讯作者：
Dolan BP