Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex

Cell Cycle. 2019 Mar-Apr;18(6-7):759-770. doi: 10.1080/15384101.2019.1593708. Epub 2019 Mar 28.

Abstract

Senescence is a tumor suppressor program characterized by a stable growth arrest while maintaining cell viability. Senescence-associated ribogenesis defects (SARD) have been shown to regulate senescence through the ability of the ribosomal protein S14 (RPS14 or uS11) to bind and inhibit the cyclin-dependent kinase 4 (CDK4). Here we report another ribosomal protein that binds and inhibits CDK4 in senescent cells: L22 (RPL22 or eL22). Enforcing the expression of RPL22/eL22 is sufficient to induce an RB and p53-dependent cellular senescent phenotype in human fibroblasts. Mechanistically, RPL22/eL22 can interact with and inhibit CDK4-Cyclin D1 to decrease RB phosphorylation both in vitro and in cells. Briefly, we show that ribosome-free RPL22/eL22 causes a cell cycle arrest which could be relevant during situations of nucleolar stress such as cellular senescence or the response to cancer chemotherapy.

Keywords: CDK4; RPL22/eL22; RPS14/uS11; Ribosome biogenesis; cyclin D1; senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology*
  • Cell Cycle Checkpoints / physiology
  • Cell Line
  • Cellular Senescence / physiology
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase 4 / metabolism*
  • HEK293 Cells
  • Humans
  • Phosphorylation / physiology
  • RNA-Binding Proteins / metabolism*
  • Retinoblastoma Protein / metabolism
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism*
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • RNA-Binding Proteins
  • Retinoblastoma Protein
  • Ribosomal Proteins
  • Tumor Suppressor Protein p53
  • ribosomal protein S14
  • RPL22 protein, human
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4

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