Lee, Sang Bae Kwon, Il-Sun Park, Jihye Lee, Kyung-Hoon Ahn, Younghee Lee, Cheolju Kim, Joon Choi, Soo Young Cho, Sung-Woo Ahn, Jee-Yin 2024-01-20T18:33:10Z 2024-01-20T18:33:10Z 2021-09-05 2010-09-17 0021-9258 https://pubs.kist.re.kr/handle/201004/131097 RPS3, a conserved, eukaryotic ribosomal protein of the 40 S subunit, is required for ribosome biogenesis. Because ribosomal proteins are abundant and ubiquitous, they may have additional extraribosomal functions. Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3. RPS3 induced neuronal apoptosis, up-regulating proapoptotic proteins Dp5/Hrk and Bim by binding to E2F1 and acting synergistically with it. Akt-dependent phosphorylation of RPS3 inhibited its proapoptotic function and perturbed its interaction with E2F1. These events coincided with nuclear translocation and accumulation of RPS3, where it functions as an endonuclease. Nuclear accumulation of RPS3 results in an increase in DNA repair activity to some extent, thereby sustaining neuronal survival. Abolishment of Akt-mediated RPS3 phosphorylation through mutagenesis accelerated apoptotic cell death and severely compromised nuclear translocation of RPS3. Thus, our findings define an extraribosomal role of RPS3 as a molecular switch that accommodates apoptotic induction to DNA repair through Akt-mediated phosphorylation. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC SYMPATHETIC NEURONS CELL-DEATH GENOTOXIC STRESS SURVIVAL DAMAGE PHOSPHORYLATION PATHWAY TRANSLOCATION EXPRESSION ACTIVATION Ribosomal Protein S3, a New Substrate of Akt, Serves as a Signal Mediator between Neuronal Apoptosis and DNA Repair Article 10.1074/jbc.M110.131367 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.38, pp.29457 - 29468 JOURNAL OF BIOLOGICAL CHEMISTRY 285 38 29457 29468 scie scopus 000281740100048 2-s2.0-77956510397 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article SYMPATHETIC NEURONS CELL-DEATH GENOTOXIC STRESS SURVIVAL DAMAGE PHOSPHORYLATION PATHWAY TRANSLOCATION EXPRESSION ACTIVATION