Symposium Theme: From Molecular Machinery to Clinical ChallengesPoster Session 3: Late Breaking Abstracts & Vendor Exhibits: no. PS3-4: abstract ISRA156Endothelial senescence is one of the earliest events during vascular aging and contributes to vascular remodeling. Sirtuin-1 (SIRT1) elicits its anti-senescent functions in part by mediating proteasome-mediated degradation of LKB1, a pro-senescent protein kinase [1], [2]. The present study was designed to investigate the molecular mechanisms underlying SIRT1-regulated LKB1 degradation by focusing on an E3 ligase, HERC2 (HECT domain and RLD 2 protein). In primary porcine aortic endothelial cells (PAECs), LKB1 degradation was significantly blocked by MG132. Western blotting revealed that LKB1 was ubiquitinated and degraded in nucleus. HERC2 was identified as the E3 ligase of LKB1. Knockdown of HERC2 enhanced the protein accumulation of LKB1 in nucleus and promoted ...postprin
