eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage

Oncogene. 2022 Apr;41(17):2431-2443. doi: 10.1038/s41388-022-02262-5. Epub 2022 Mar 12.


eIF3a (eukaryotic translation initiation factor 3a), a subunit of the eIF3 complex, has been suggested to play a regulatory role in protein synthesis and in cellular response to DNA-damaging treatments. S6K1 is an effector and a mediator of mTOR complex 1 (mTORC1) in regulating protein synthesis and integrating diverse signals into control of cell growth and response to stress. Here, we show that eIF3a regulates S6K1 activity by inhibiting mTORC1 kinase via regulating Raptor synthesis. The regulation of Raptor synthesis is via eIF3a interaction with HuR (human antigen R) and binding of the eIF3a-HuR complex to the 5'-UTR of Raptor mRNA. Furthermore, mTORC1 may mediate eIF3a function in cellular response to cisplatin by regulating synthesis of NER proteins and NER activity. Taken together, we conclude that the mTOR signaling pathway may also be regulated by translational control and mediate eIF3a regulation of cancer cell response to cisplatin by regulating NER protein synthesis.

MeSH terms

  • 5' Untranslated Regions
  • Cisplatin* / pharmacology
  • DNA Damage / genetics
  • ELAV-Like Protein 1* / genetics
  • Eukaryotic Initiation Factor-3* / genetics
  • Eukaryotic Initiation Factor-3* / metabolism
  • Humans
  • Mechanistic Target of Rapamycin Complex 1* / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism


  • 5' Untranslated Regions
  • EIF3A protein, human
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Eukaryotic Initiation Factor-3
  • MTOR protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Cisplatin