SIRT1 ubiquitination is regulated by opposing activities of APC/C-Cdh1 and AROS during stress-induced premature senescence

Experimental & Molecular Medicine, Published online: 01 June 2023; doi:10.1038/s12276-023-01012-1Two opposing molecular mechanisms determine the stability of SIRT1, a protein that prevents cells from prematurely entering the ‘retirement’ state known as senescence. This state, in which cell division is halted and tissue repair and regeneration impeded, is a natural endpoint of aging but also arises from cellular damage and other stressors. South Korean researchers led by Eun-Joo Kim at Dankook University, Cheonan, and Soo-Jong Um at Sejong University, Seoul, have identified two proteins that govern the onset of senescence by affecting SIRT1’s stability. One promotes the addition of chemical modifications to SIRT1 that mark it for destruction, while the other prevents such modifications. The researchers further showed that a drug that tips the balance in favor of SIRT1 stabilization could prevent early senescence in an animal model of pulmonary fibrosis, a currently incurable lung disorder.
Source: Experimental and Molecular Medicine - Category: Molecular Biology Authors: Source Type: research