CHIP E3 ligase regulates mammalian senescence by modulating the levels of oxidized proteins.

Senescence can be induced by various stressors including oxidative stress. It has been reported that CHIP (C-terminus of Hsp70-interacting protein) ligase is induced during senescence while CHIP(-/-) mice exhibit accelerated aging. Here, we explore the effects of modulating CHIP expression on mammalian senescence. We demonstrate that CHIP silencing induces premature senescence that is accompanied by elevated levels of oxidized proteins. On the contrary, ectopic expression of CHIP leads to oxidized proteins levels reduction. Moreover, we reveal that CHIP(-/-) mouse fibroblasts have an impaired ubiquitin proteasome system. Taken together, we propose that CHIP influences cellular senescence by modulating the oxidative load.