F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis
Chronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent i...
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.599020/full |
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| author | Tiao Li Tiao Li Tiao Li Xue He Xue He Xue He Lijuan Luo Lijuan Luo Lijuan Luo Huihui Zeng Huihui Zeng Huihui Zeng Siying Ren Siying Ren Siying Ren Yan Chen Yan Chen Yan Chen |
| author_facet | Tiao Li Tiao Li Tiao Li Xue He Xue He Xue He Lijuan Luo Lijuan Luo Lijuan Luo Huihui Zeng Huihui Zeng Huihui Zeng Siying Ren Siying Ren Siying Ren Yan Chen Yan Chen Yan Chen |
| author_sort | Tiao Li |
| collection | DOAJ |
| description | Chronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent inflammation and epithelial apoptosis induced by cigarette smoke would be extremely beneficial for improving the treatment and prevention of COPD. A histone methyl modifier, protein arginine N-methyltransferase 6 (PRMT6), is reported to alleviate cigarette smoke extract (CSE)-induced emphysema through inhibiting inflammation and cell apoptosis. However, few studies have focused on the modulation of PRMT6 in regulating inflammation and cell apoptosis. In this study, we showed that protein expression of PRMT6 was aberrantly decreased in the lung tissue of COPD patients and CSE-treated epithelial cells. FBXW17, a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases, selectively bound to PRMT6 in nuclei to modulate its elimination in the proteasome system. Proteasome inhibitor or silencing of FBXW17 abrogated CSE-induced PRMT6 protein degradation. Furthermore, negative alteration of FBXW17/PRMT6 signaling lessened the proapoptotic and proinflammatory effects of CSE in lung epithelial cells. Our study, therefore, provides a potential therapeutic target against the airway inflammation and cell death in CS-induced COPD. |
| first_indexed | 2024-12-14T22:21:59Z |
| format | Article |
| id | doaj.art-476b94d8cc654235aa53a107834dafde |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T22:21:59Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-476b94d8cc654235aa53a107834dafde2022-12-21T22:45:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-04-01910.3389/fcell.2021.599020599020F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and ApoptosisTiao Li0Tiao Li1Tiao Li2Xue He3Xue He4Xue He5Lijuan Luo6Lijuan Luo7Lijuan Luo8Huihui Zeng9Huihui Zeng10Huihui Zeng11Siying Ren12Siying Ren13Siying Ren14Yan Chen15Yan Chen16Yan Chen17Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaDepartment of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaDepartment of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaDepartment of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaDepartment of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaDepartment of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, ChinaResearch Unit of Respiratory Disease, Central South University, Changsha, ChinaDiagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, ChinaChronic obstructive pulmonary disease (COPD) is a chronic debilitating lung disease, characterized by progressive airway inflammation and lung structural cell death. Cigarette smoke is considered the most common risk factor of COPD pathogenesis. Understanding the molecular mechanisms of persistent inflammation and epithelial apoptosis induced by cigarette smoke would be extremely beneficial for improving the treatment and prevention of COPD. A histone methyl modifier, protein arginine N-methyltransferase 6 (PRMT6), is reported to alleviate cigarette smoke extract (CSE)-induced emphysema through inhibiting inflammation and cell apoptosis. However, few studies have focused on the modulation of PRMT6 in regulating inflammation and cell apoptosis. In this study, we showed that protein expression of PRMT6 was aberrantly decreased in the lung tissue of COPD patients and CSE-treated epithelial cells. FBXW17, a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases, selectively bound to PRMT6 in nuclei to modulate its elimination in the proteasome system. Proteasome inhibitor or silencing of FBXW17 abrogated CSE-induced PRMT6 protein degradation. Furthermore, negative alteration of FBXW17/PRMT6 signaling lessened the proapoptotic and proinflammatory effects of CSE in lung epithelial cells. Our study, therefore, provides a potential therapeutic target against the airway inflammation and cell death in CS-induced COPD.https://www.frontiersin.org/articles/10.3389/fcell.2021.599020/fullapoptosisinflammationcigarette smoke extractprotein arginine methyltransferase 6 (PRMT6)FBXW17chronic obstructive pulmonary disease |
| spellingShingle | Tiao Li Tiao Li Tiao Li Xue He Xue He Xue He Lijuan Luo Lijuan Luo Lijuan Luo Huihui Zeng Huihui Zeng Huihui Zeng Siying Ren Siying Ren Siying Ren Yan Chen Yan Chen Yan Chen F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis Frontiers in Cell and Developmental Biology apoptosis inflammation cigarette smoke extract protein arginine methyltransferase 6 (PRMT6) FBXW17 chronic obstructive pulmonary disease |
| title | F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis |
| title_full | F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis |
| title_fullStr | F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis |
| title_full_unstemmed | F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis |
| title_short | F-Box Protein FBXW17-Mediated Proteasomal Degradation of Protein Methyltransferase PRMT6 Exaggerates CSE-Induced Lung Epithelial Inflammation and Apoptosis |
| title_sort | f box protein fbxw17 mediated proteasomal degradation of protein methyltransferase prmt6 exaggerates cse induced lung epithelial inflammation and apoptosis |
| topic | apoptosis inflammation cigarette smoke extract protein arginine methyltransferase 6 (PRMT6) FBXW17 chronic obstructive pulmonary disease |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.599020/full |
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