UFMylation maintains YAP stability to promote vascular endothelial cell senescence
Yanan Liu,
Min Zuo,
Aiwei Wu,
Zhaoxiang Wang,
Siting Wang,
Yongping Bai,
Junzhi Zhou,
Hu Wang
Affiliations
Yanan Liu
Department 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, China
Min Zuo
Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, China
Aiwei Wu
Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, Hangzhou 311121, China
Zhaoxiang Wang
School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
Siting Wang
Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
Yongping Bai
Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Corresponding author
Junzhi Zhou
School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China; Corresponding author
Hu Wang
Key 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 author
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.
