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Disorder at the Start: The Contribution of Dysregulated Translation Initiation to Cancer Therapy Resistance

Gulshan Sunavala-Dossabhoy1

  • 1Department of Biochemistry and Molecular Biology, Louisiana State University Health and Feist Weiller Cancer Center, Shreveport, LA, United States.

Frontiers in Oral Health
|January 20, 2022
PubMed

Insights

Cellular RNA translation into protein is regulated and essential for cell function. Deregulation of this process, particularly at the Tousled-like kinase 1 (TLK1) gene, contributes to cancer and treatment resistance.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Cellular RNA translation into protein is a fundamental, energy-intensive process.
  • This translation is tightly regulated by extracellular signals and intracellular amino acid availability.
  • The 5' methyl 7-guanosine (m7G) cap is crucial for mRNA recruitment of the translation machinery in eukaryotes.

Purpose of the Study:

  • To provide an overview of mammalian translation initiation.
  • To discuss the primary regulatory mechanisms of translation.
  • To explore how deregulation of translation initiation contributes to tumorigenesis and treatment resistance, focusing on TLK1.

Main Methods:

  • Literature review of mammalian translation initiation.
  • Analysis of regulatory mechanisms governing translation.
  • Discussion of the role of aberrant translation initiation in cancer, specifically TLK1 downstream ORF initiation.

Main Results:

  • Translation initiation is a key regulatory point in gene expression.
  • Dysregulation of translation initiation is implicated in cancer development.
  • Initiation at a downstream open reading frame (ORF) of Tousled-like kinase 1 (TLK1) is linked to cancer treatment resistance.

Conclusions:

  • Understanding translation initiation regulation is vital for cancer biology.
  • Aberrant translation control, exemplified by TLK1, represents a significant mechanism in tumorigenesis and therapeutic failure.
  • Targeting translation initiation pathways may offer novel cancer treatment strategies.
Keywords:
4EBPTLK1cap-dependenteIF2eIF2AeIF4AeIF4Etranslation

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