PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)

Nucleic Acids Res. 2020 Dec 16;48(22):12900-12916. doi: 10.1093/nar/gkaa1108.


PDCD2 is an evolutionarily conserved protein with previously characterized homologs in Drosophila (zfrp8) and budding yeast (Tsr4). Although mammalian PDCD2 is essential for cell proliferation and embryonic development, the function of PDCD2 that underlies its fundamental cellular role has remained unclear. Here, we used quantitative proteomics approaches to define the protein-protein interaction network of human PDCD2. Our data revealed that PDCD2 specifically interacts with the 40S ribosomal protein uS5 (RPS2) and that the PDCD2-uS5 complex is assembled co-translationally. Loss of PDCD2 expression leads to defects in the synthesis of the small ribosomal subunit that phenocopy a uS5 deficiency. Notably, we show that PDCD2 is important for the accumulation of soluble uS5 protein as well as its incorporation into 40S ribosomal subunit. Our findings support that the essential molecular function of PDCD2 is to act as a dedicated ribosomal protein chaperone that recognizes uS5 co-translationally in the cytoplasm and accompanies uS5 to ribosome assembly sites in the nucleus. As most dedicated ribosomal protein chaperones have been identified in yeast, our study reveals that similar mechanisms exist in human cells to assist ribosomal proteins coordinate their folding, nuclear import and assembly in pre-ribosomal particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Nucleus / genetics
  • Conserved Sequence / genetics
  • HeLa Cells
  • Humans
  • Molecular Chaperones / genetics*
  • Ribosomal Proteins / genetics*
  • Ribosome Subunits, Small, Eukaryotic / genetics
  • Ribosomes / genetics*
  • Saccharomyces cerevisiae / genetics


  • Apoptosis Regulatory Proteins
  • Molecular Chaperones
  • PDCD2 protein, human
  • RPS2 protein, human
  • Ribosomal Proteins