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

Sang Bae Lee, Il Sun Kwon, Jihye Park, Kyung Hoon Lee, Younghee Ahn, Cheolju Lee, Joon Kim, Soo Young Choi, Sung Woo Cho, Jee Yin Ahn

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)29457-29468
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number38
DOIs
Publication statusPublished - 2010 Sep 17

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Phosphorylation
DNA Repair
Repair
Apoptosis
DNA
Substrates
Mutagenesis
Ribosomal Proteins
Endonucleases
Nerve Growth Factor
Cell death
Threonine
Ribosomes
Cell Death
Phosphotransferases
Switches
ribosomal protein S3
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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

In: Journal of Biological Chemistry, Vol. 285, No. 38, 17.09.2010, p. 29457-29468.

Research output: Contribution to journalArticle

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. / Ribosomal protein S3, a new substrate of Akt, serves as a signal mediator between neuronal apoptosis and DNA repair. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 38. pp. 29457-29468.
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