UFMylation maintains YAP stability to promote vascular endothelial cell senescence
Summary: Endothelial cell (EC) senescence is an accomplice for vascular aging, which leads to cardiovascular diseases (CVDs). Evidences showed that Hippo-Yes-associated protein (YAP) signaling pathway plays an essential role in aging-associated CVDs. Here, we reported that YAP was elevated in senesc...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001142 |
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| author | Yanan Liu Min Zuo Aiwei Wu Zhaoxiang Wang Siting Wang Yongping Bai Junzhi Zhou Hu Wang |
| author_facet | Yanan Liu Min Zuo Aiwei Wu Zhaoxiang Wang Siting Wang Yongping Bai Junzhi Zhou Hu Wang |
| author_sort | Yanan Liu |
| collection | DOAJ |
| description | Summary: Endothelial cell (EC) senescence is an accomplice for vascular aging, which leads to cardiovascular diseases (CVDs). Evidences showed that Hippo-Yes-associated protein (YAP) signaling pathway plays an essential role in aging-associated CVDs. Here, we reported that YAP was elevated in senescent human umbilical vein endothelial cells (HUVECs) and inhibition of YAP could attenuate HUVECs senescence. Besides, our findings revealed that the activity of UFMylation and the level of YAP were both elevated in senescent cells. Furthermore, UFM1-modified YAP was upregulated in senescent ECs, and increased the stability of YAP. Importantly, we found that compound 8.5, an inhibitor of E1 of UFMylation, can alleviate vascular aging in aged mice. Together, our finding provides molecular mechanism by which UFMylation maintains YAP stability and exerts an important role in promoting cell senescence, and identified that a previously unrecognized UFMylation is a potential therapeutic target for anti-aging. |
| format | Article |
| id | doaj-art-be24af6230a94430b01bdb6169456b69 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-be24af6230a94430b01bdb6169456b692025-02-05T04:32:31ZengElsevieriScience2589-00422025-02-01282111854UFMylation maintains YAP stability to promote vascular endothelial cell senescenceYanan Liu0Min Zuo1Aiwei Wu2Zhaoxiang Wang3Siting Wang4Yongping Bai5Junzhi Zhou6Hu Wang7Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, ChinaKey Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, ChinaKey Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, ChinaSchool of Basic Medicine, Guangdong Medical University, Dongguan 523808, ChinaDepartment of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, ChinaDepartment of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Corresponding authorSchool of Basic Medicine, Guangdong Medical University, Dongguan 523808, China; Corresponding authorKey Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, China; Corresponding authorSummary: Endothelial cell (EC) senescence is an accomplice for vascular aging, which leads to cardiovascular diseases (CVDs). Evidences showed that Hippo-Yes-associated protein (YAP) signaling pathway plays an essential role in aging-associated CVDs. Here, we reported that YAP was elevated in senescent human umbilical vein endothelial cells (HUVECs) and inhibition of YAP could attenuate HUVECs senescence. Besides, our findings revealed that the activity of UFMylation and the level of YAP were both elevated in senescent cells. Furthermore, UFM1-modified YAP was upregulated in senescent ECs, and increased the stability of YAP. Importantly, we found that compound 8.5, an inhibitor of E1 of UFMylation, can alleviate vascular aging in aged mice. Together, our finding provides molecular mechanism by which UFMylation maintains YAP stability and exerts an important role in promoting cell senescence, and identified that a previously unrecognized UFMylation is a potential therapeutic target for anti-aging.http://www.sciencedirect.com/science/article/pii/S2589004225001142Biological sciencesBiochemistryCell biologyCell |
| spellingShingle | Yanan Liu Min Zuo Aiwei Wu Zhaoxiang Wang Siting Wang Yongping Bai Junzhi Zhou Hu Wang UFMylation maintains YAP stability to promote vascular endothelial cell senescence iScience Biological sciences Biochemistry Cell biology Cell |
| title | UFMylation maintains YAP stability to promote vascular endothelial cell senescence |
| title_full | UFMylation maintains YAP stability to promote vascular endothelial cell senescence |
| title_fullStr | UFMylation maintains YAP stability to promote vascular endothelial cell senescence |
| title_full_unstemmed | UFMylation maintains YAP stability to promote vascular endothelial cell senescence |
| title_short | UFMylation maintains YAP stability to promote vascular endothelial cell senescence |
| title_sort | ufmylation maintains yap stability to promote vascular endothelial cell senescence |
| topic | Biological sciences Biochemistry Cell biology Cell |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001142 |
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