DPP8/9 are not Required to Cleave Most Proline-Containing Peptides.
DPP8/9 are not Required to Cleave Most Proline-Containing Peptides.
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切割大多数含脯氨酸的肽不需要 DPP8/9。
DOI：
10.1002/ijch.202200117
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发表时间：
2023
影响因子：
3.2
通讯作者：
Bachovchin,DanielA
中科院分区：
文献类型：
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作者：
Bhattacharjee,Abir;Bachovchin,DanielA
细胞内丝氨酸肽酶DPP8和DPP9的小分子抑制剂(DPP8/9)可激活NLRP1和CARD8炎症体，但关键的DPP8/9底物尚未确定。DPP8/9在Pro之后裂解，从多肽或蛋白质中去除N-末端二肽，使用伪肽报告底物的研究表明，这些酶可能在蛋白酶体产生的许多含Pro的多肽的分解代谢中发挥关键作用。在这里，我们评估了细胞裂解物中广泛的实际多肽的降解，并发现DPP8/9实际上并不参与绝大多数含有Pro的多肽的加工。总体而言，这些结果表明，DPP8/9的底物范围比之前认为的要有限得多，可能特异性地切割了一些至关重要但尚不清楚的细胞内肽或蛋白，以调节炎症小体的激活。
Small molecule inhibitors of the intracellular serine peptidases DPP8 and DPP9 (DPP8/9) activate the NLRP1 and CARD8 inflammasomes, but the key DPP8/9 substrates have not yet been identified. DPP8/9 cleave after proline to remove N‐terminal dipeptides from peptides or proteins, and studies using pseudo‐peptide reporter substrates have suggested that these enzymes may play key roles in the catabolism of many proline‐containing peptides generated by the proteasome. Here, we evaluated the degradation of a wide array of actual peptides in cell lysates, and discovered that DPP8/9 are not in fact involved in the processing of the vast majority of proline‐containing peptides. Overall, these results indicate that DPP8/9 have a much more limited substrate scope than previously thought, and likely specifically cleave some critically important, but as yet unknown, intracellular peptide or protein that regulates inflammasome activation.