https://scholars.lib.ntu.edu.tw/handle/123456789/616020
標題: | Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence | 作者: | Liao, Chia-Li Hu, Rong-Chi Liao, Min-Shiang Chen, Yi-Ju Chen, Ya-Ping Hsieh, Hsi-Hsien Tai, Chih-Hsuan Chou, Tzyy-Chao Chu, Chi-Yuan Chen, Yu-Ju Lo, Lee-Chiang JING-JER LIN |
關鍵字: | Activity-based probe; Benzylphosphonofluoridate; Senescence; Serine hydrolase; TPP | 公開日期: | 2022 | 卷: | 135 | 期: | 10 | 來源出版物: | Journal of cell science | 摘要: | Tripeptidyl peptidase II (TPPII or TPP2) degrades N-terminal tripeptides from proteins and peptides. Studies in both humans and mice have shown that TPPII deficiency is linked to cellular immune-senescence, lifespan regulation and the aging process. However, the mechanism of how TPPII participates in these processes is less clear. In this study, we established a chemical probe-based assay and found that although the mRNA and protein levels of TPPII were not altered during senescence, its enzymatic activity was reduced in senescent human fibroblasts. We also showed that elevation of the levels of the serine protease inhibitor serpinB2 reduced TPPII activity in senescent cells. Moreover, suppression of TPPII led to elevation in the amount of lysosomal contents as in well as TPPI (TPP1) and β-galactosidase activities, suggesting that lysosome biogenesis is induced to compensate for the reduction of TPPII activity in senescent cells. Together, this study discloses a critical role of the serpinB2-TPPII signaling pathway in proteostasis during senescence. Since serpinB2 levels can be increased by a variety of cellular stresses, reduction of TPPII activity through activation of serpinB2 might represent a common pathway for cells to respond to different stress conditions. This article has an associated First Person interview with the first author of the paper. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/616020 | ISSN: | 0021-9533 1477-9137 |
DOI: | 10.1242/jcs.259513 |
顯示於: | 生物化學暨分子生物學科研究所 |
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