The Cytoplasmic Peptidase DPP9 Is Rate-limiting for Degradation of Proline-containing Peptides
The Cytoplasmic Peptidase DPP9 Is Rate-limiting for Degradation of Proline-containing Peptides
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DOI：
10.1074/jbc.m109.041871
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发表时间：
2009-10-02
影响因子：
4.8
通讯作者：
Melchior, Frauke
中科院分区：
文献类型：
--
作者：
Geiss-Friedlander, Ruth;Parmentier, Nicolas;Melchior, Frauke
蛋白质降解是所有活细胞中不断发生的重要过程。大多数细胞蛋白的调节降解是由蛋白酶体启动的，蛋白酶体产生不同长度的肽。这些肽被细胞质肽酶迅速切割成单个氨基酸。含有脯氨酸的肽由于吡咯烷环的结构限制而造成了一个特殊的问题，这种结构限制阻止了大多数肽酶的裂解。在这里，我们表明DPP9是一种特征不明显的细胞质脯氨酸肽酶，在细胞提取物和完整细胞中对含有脯氨酸的底物的破坏具有限速作用。我们确定了DPP9的第一个天然底物，RU1（34-42）抗原肽（VPYGSFKHV）。RU1（34-42）在体外被DPP9降解，完整细胞中DPP9的下调导致该抗原的呈递增加。总之，我们的发现证明了DPP9在肽转换和抗原呈递中的重要作用。
Protein degradation is an essential process that continuously takes place in all living cells. Regulated degradation of most cellular proteins is initiated by proteasomes, which produce peptides of varying length. These peptides are rapidly cleaved to single amino acids by cytoplasmic peptidases. Proline-containing peptides pose a specific problem due to structural constrains imposed by the pyrrolidine ring that prevents most peptidases from cleavage. Here we show that DPP9, a poorly characterized cytoplasmic prolyl-peptidase, is rate-limiting for destruction of proline-containing substrates both in cell extracts and in intact cells. We identified the first natural substrate for DPP9, the RU1(34-42) antigenic peptide (VPYGSFKHV). RU1(34-42) is degraded in vitro by DPP9, and down-regulation of DPP9 in intact cells results in increased presentation of this antigen. Together our findings demonstrate an important role for DPP9 in peptide turnover and antigen presentation.