Related Experiment Video

Updated: May 7, 2026

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
10:24

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources

Published on: January 27, 2026

Small-Molecule targeting of translation initiation for cancer therapy

Bertal H Aktas1, Yuan Qiao, Esra Ozdelen

  • 1Department of Medicine, Brigham and Women's Hospital, Boston.

Oncotarget
|October 5, 2013
PubMed

Insights

Small molecules that inhibit translation initiation by inducing eIF2α phosphorylation reduce cancer cell proliferation and tumor growth. This targeted approach offers a new strategy for mechanism-specific anti-cancer drug development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Translation initiation is a key regulatory step in cell growth and cancer development.
  • The eIF2.GTP.Met-tRNAi ternary complex is crucial for initiating protein synthesis.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting translation initiation in cancer.
  • To explore the effects of small molecules inducing eIF2α phosphorylation on cancer cells and tumors.

Main Methods:

  • Utilized small-molecular-weight compounds to induce eIF2α phosphorylation.
  • Assessed the impact on the eIF2.GTP.Met-tRNAi ternary complex availability.
  • Evaluated cancer cell proliferation in vitro and tumor growth in vivo.
  • Analyzed gene expression changes, including growth-promoting and ER stress response genes.

Main Results:

  • Inhibition of translation initiation restricted the ternary complex, abrogating cancer cell proliferation and tumor growth.
  • Preferential downregulation of growth-promoting proteins and upregulation of ER stress response genes were observed.
  • These effects were consistent in cancer cells and tumors from both animal models and human patients.

Conclusions:

  • Small molecules targeting translation initiation factors show promise as anti-cancer agents.
  • This study provides direct in vivo evidence for small molecule-mediated translational control of gene expression.
  • Translation initiation factors are validated targets for developing mechanism-specific anti-cancer therapies.

More Related Videos

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling10:59

Analysis of Translation Initiation During Stress Conditions by Polysome Profiling

Published on: May 19, 2014

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs10:37

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

Related Concept Videos

Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Initiation of Translation02:33

Initiation of Translation

Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life