RGD Reference Report - Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. - Rat Genome Database

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Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair.

Authors: Lee, SB  Kwon, IS  Park, J  Lee, KH  Ahn, Y  Lee, C  Kim, J  Choi, SY  Cho, SW  Ahn, JY 
Citation: Lee SB, etal., J Biol Chem. 2010 Sep 17;285(38):29457-68. doi: 10.1074/jbc.M110.131367. Epub 2010 Jul 6.
RGD ID: 10402036
Pubmed: PMID:20605787   (View Abstract at PubMed)
PMCID: PMC2937978   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.131367   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleus located_inIDA 10402036; 10402036PMID:20605787UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kinase binding enablesIPIUniProtKB:P4719610402036PMID:20605787UniProt 
protein binding enablesIPIUniProtKB:P6290910402036PMID:20605787UniProt 
protein binding enablesIPIUniProtKB:P2339610402036PMID:20605787UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
E2f1  (E2F transcription factor 1)
Ngf  (nerve growth factor)
Rps3  (ribosomal protein S3)


Additional Information