PDCD4 controls the G1/S-phase transition in a telomerase-immortalized epithelial cell line and affects the expression level and translation of multiple mRNAs

Sci Rep. 2020 Feb 17;10(1):2758. doi: 10.1038/s41598-020-59678-w.


PDCD4, the protein encoded by the tumor suppressor gene PDCD4 (programmed cell death 4) has been implicated in the control of cellular transcription and translation by modulating the activity of specific transcription factors and suppressing the translation of mRNAs with structured 5'-UTRs. Most studies of human PDCD4 have employed tumor cell lines, possibly resulting in a biased picture of its role in normal cells. Here, we have studied the function of PDCD4 in a telomerase-immortalized human epithelial cell line. We show for the first time that PDCD4 is required for the G1/S-transition, demonstrating its crucial role in the cell cycle. Inhibition of p53-dependent activation of p21WAF1/CIP1 overrides the requirement for PDCD4 for the G1/S-transition, suggesting that PDCD4 counteracts basal p53 activity to prevent activation of the G1/S checkpoint by p53. Transcriptome and ribosome profiling data show that silencing of PDCD4 changes the expression levels and translation of many mRNAs, providing an unbiased view of the cellular processes that are affected by PDCD4 in an epithelial cell line. Our data identify PDCD4 as a key regulator of cell cycle- and DNA-related functions that are inhibited when it is silenced, suggesting that decreased expression of PDCD4 might contribute to tumor development by compromising genomic integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Line, Transformed
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Protein Biosynthesis*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Signal Transduction
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Transcriptome*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • 5' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • PDCD4 protein, human
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • TERT protein, human
  • Telomerase