https://scholars.lib.ntu.edu.tw/handle/123456789/617818
標題: | Reduced symmetric dimethylation stabilizes vimentin and promotes metastasis in MTAP-deficient lung cancer | 作者: | Chang, Wen-Hsin Chen, Yi-Ju Hsiao, Yi-Jing Chiang, Ching-Cheng Wang, Chia-Yu Chang, Ya-Ling Hong, Qi-Sheng Lin, Chien-Yu Lin, Shr-Uen Chang, Gee-Chen Chen, Hsuan-Yu Chen, Yu-Ju Chen, Ching-Hsien PAN-CHYR YANG SUNG-LIANG YU |
關鍵字: | Methylproteome; Methylthioadenosine (MTA); Post-translational modification (PTM); Protein arginine methyltransferase 5 (PRMT5); Symmetric dimethylarginine (sDMA) | 公開日期: | 3-八月-2022 | 出版社: | WILEY | 卷: | 23 | 期: | 8 | 來源出版物: | EMBO reports | 摘要: | The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/617818 | ISSN: | 1469-221X | DOI: | 10.15252/embr.202154265 |
顯示於: | 醫學檢驗暨生物技術學系 |
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