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Proteomic profiling of eIF3a conditional knockout mice.

Wei Zhuo1,2, Juan Chen3, Shilong Jiang3

  • 1Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Molecular Biosciences
|May 8, 2023
PubMed
Summary
This summary is machine-generated.

Eukaryotic translation initiation factor 3 subunit A (eIF3a) is essential for life. Its absence causes abnormal tissue pathology and alters numerous proteins involved in diverse cellular functions beyond translation.

Keywords:
eIF3aknockout miceoxidative stressprotein landscapeproteomics

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Eukaryotic translation initiation factor 3 subunit A (eIF3a) is a key component of the eIF3 complex, crucial for protein biosynthesis.
  • eIF3a's role in tumor development and its regulated proteins are not fully understood.
  • Understanding eIF3a's in vivo functions is critical for cancer research and therapeutic strategies.

Purpose of the Study:

  • To investigate the essentiality of eIF3a for organismal survival using a conditional knockout mouse model.
  • To identify and characterize proteins differentially expressed in various tissues upon eIF3a ablation.
  • To explore the functional and pathway implications of eIF3a-regulated proteins through bioinformatics analysis.

Main Methods:

  • Generation of eIF3a conditional knockout mice using a Cre-loxP system.
  • Tandem mass tag (TMT) labeling coupled with LC-MS/MS analysis for quantitative proteomic profiling.
  • Bioinformatics analysis, including KEGG pathway enrichment, to interpret functional roles of differentially expressed proteins.

Main Results:

  • eIF3a is essential for life; knockout mice exhibited abnormal tissue pathology in multiple organs (lungs, fat, skin, spleen, thymus).
  • Significant numbers of tissue-specific differentially expressed proteins (DEPs) were identified in eIF3a knockout mice (e.g., 588 in lungs, 944 in spleen).
  • Bioinformatics analysis revealed eIF3a's involvement in diverse functions including cellular signaling, immune response, metabolism, DNA replication, and pathways related to oxidative stress and ferroptosis.

Conclusions:

  • eIF3a is indispensable for sustaining life, highlighting its fundamental role in cellular homeostasis.
  • The study uncovers novel, diverse functions of eIF3a's downstream proteins beyond canonical mRNA translational regulation.
  • These findings provide new insights into eIF3a's broader biological significance and potential as a therapeutic target.