Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in

Hongyan Li1,2,3,4,5,6, Hong Zhang7,8,9,10,11,12, Guomin Huang1,3,4,5,6,13

  • 1Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.

Abstract

Insights

Ribosomal protein S27a (RPS27a) binds ribosomal protein L11 (RPL11), inhibiting p53 degradation in lung adenocarcinoma. RPS27a knockdown suppresses tumor growth, suggesting it as a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Ribosomal proteins (RPs) can activate p53, particularly ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11).
  • Understanding the link between RPs and p53 activation is crucial for cancer research.

Purpose of the Study:

  • To investigate the interaction between ribosomal proteins and RPL11.
  • To determine the role of ribosomal protein S27a (RPS27a) in p53 activation within lung adenocarcinoma (LUAD) cells.

Main Methods:

  • Proteomics and immunoprecipitation to identify RPL11-binding proteins.
  • GST pull-down and co-immunoprecipitation assays to analyze protein interactions.
  • In vitro ubiquitination, cell cycle, apoptosis, invasion, migration, viability, and colony formation assays to assess functional effects.
  • TCGA dataset analysis and immunohistochemistry to evaluate RPS27a expression in LUAD.

Main Results:

  • RPS27a was identified as a novel RPL11-binding protein, directly interacting with RPL11.
  • RPS27a knockdown enhanced RPL11-MDM2 binding, inhibiting MDM2-mediated p53 ubiquitination and degradation, thus stabilizing p53.
  • RPS27a upregulation in LUAD correlated with tumor progression, poorer prognosis, and elevated p53, MDM2, and RPL11 levels. RPS27a knockdown suppressed tumor xenograft formation.

Conclusions:

  • RPS27a interacts with RPL11 and modulates p53 stability by affecting MDM2-mediated degradation.
  • RPS27a plays a significant role in LUAD progression and prognosis.
  • RPS27a represents a potential therapeutic target for lung adenocarcinoma.

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