YAP inhibits vascular calcification by promoting Beclin1 ubiquitination and autophagy
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Updated: Oct 31, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Chengwei Wang1, Yijun Sun1, Huixia Lu1
1Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Jinan, China; National Key Laboratory for Innovation and Transformation of Luobing Theory, Qilu Hospital of Shandong University, Jinan, China.
Background:
Chronic kidney disease (CKD) is a major public health burden with high mortality. Vascular calcification(VC) is a critical pathological hallmark of CKD. Effective preventing and treating of VC are essential to reduce cardiovascular events in CKD patients. Recent studies have suggested a link between Yes-associated protein(YAP) and VC, but the underlying mechanisms remain poorly defined.
Objective:
To elucidate the molecular mechanisms by which YAP ameliorates VC and to identify novel therapeutic targets.
Results:
In a rat CKD model and in vascular smooth muscle cells (VSMCs) stimulated with high phosphate in vitro, YAP expression was markedly reduced. YAP overexpression ameliorated vascular wall injury, calcium salt deposition, and osteogenic transformation of VSMCs in CKD rats. Mechanistically, YAP bound to TRAF6 to promote Beclin1 ubiquitination, thereby disrupting Beclin1-Bcl2 interaction, enhancing autophagy, and suppressing VC.
Conclusion:
YAP attenuates CKD-associated VC by promoting VSMC autophagy through ubiquitination of Beclin1 and inhibition of its bingding to Bcl2.
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