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首页> 美国卫生研究院文献>The Journal of Biological Chemistry >Pseudomonas aeruginosa Cif Protein Enhances the Ubiquitination and Proteasomal Degradation of the Transporter Associated with Antigen Processing (TAP) and Reduces Major Histocompatibility Complex (MHC) Class I Antigen Presentation
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Pseudomonas aeruginosa Cif Protein Enhances the Ubiquitination and Proteasomal Degradation of the Transporter Associated with Antigen Processing (TAP) and Reduces Major Histocompatibility Complex (MHC) Class I Antigen Presentation

机译：铜绿假单胞菌Cif蛋白增强与抗原加工（TAP）相关的转运蛋白的泛素化和蛋白酶体降解并减少主要的组织相容性复合物（MHC）I类抗原呈递。

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摘要

Cif (PA2934), a bacterial virulence factor secreted in outer membrane vesicles by Pseudomonas aeruginosa, increases the ubiquitination and lysosomal degradation of some, but not all, plasma membrane ATP-binding cassette transporters (ABC), including the cystic fibrosis transmembrane conductance regulator and P-glycoprotein. The goal of this study was to determine whether Cif enhances the ubiquitination and degradation of the transporter associated with antigen processing (TAP1 and TAP2), members of the ABC transporter family that play an essential role in antigen presentation and intracellular pathogen clearance. Cif selectively increased the amount of ubiquitinated TAP1 and increased its degradation in the proteasome of human airway epithelial cells. This effect of Cif was mediated by reducing USP10 deubiquitinating activity, resulting in increased polyubiquitination and proteasomal degradation of TAP1. The reduction in TAP1 abundance decreased peptide antigen translocation into the endoplasmic reticulum, an effect that resulted in reduced antigen available to MHC class I molecules for presentation at the plasma membrane of airway epithelial cells and recognition by CD8+ T cells. Cif is the first bacterial factor identified that inhibits TAP function and MHC class I antigen presentation.
机译：Cif（PA2934）是一种由铜绿假单胞菌分泌在外膜囊泡中的细菌致病因子，它会增加某些（但不是全部）质膜ATP结合盒转运蛋白（ABC）的泛素化和溶酶体降解，包括囊性纤维化跨膜电导调节剂和P-糖蛋白。这项研究的目的是确定Cif是否增强与抗原加工相关的转运蛋白（TAP1和TAP2）的泛素化和降解，ABC转运蛋白家族的成员在抗原呈递和细胞内病原体清除中起重要作用。 Cif有选择地增加泛素化TAP1的量并增加其在人气道上皮细胞蛋白酶体中的降解。 Cif的这种作用是通过降低USP10去泛素化活性来介导的，从而导致TAP1的多泛素化和蛋白酶体降解增加。 TAP1丰度的减少会减少肽抗原向内质网的转运，这种作用导致MHC I类分子可用于呈递于气道上皮细胞质膜并被CD8 + T识别的抗原减少细胞。 Cif是确定的第一个抑制TAP功能和MHC I类抗原呈递的细菌因子。

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