Apolipoprotein B: from editosome to proteasome.

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Apolipoprotein B (apoB) is the protein component of low-density lipoproteins (LDLs).
• Early research focused on apoB's physical-chemical properties due to its large size and insolubility.
• Understanding apoB's molecular weight and structure was a significant challenge for decades.

Purpose of the Study:

• To review major advancements in apoB research over the last 10-15 years.
• To highlight breakthroughs in apoB structure, function, and expression.
• To discuss the discovery and implications of RNA editing and apoB intracellular degradation.

Main Methods:

• cDNA cloning and direct peptide sequencing for apoB-100 primary structure elucidation.
• Analysis of apoB function in vivo using transgenic and knockout animal models.
• Identification and cloning of microsomal triglyceride transfer protein (MTP) and APOBEC-1.

Main Results:

• Discovery of two apoB forms: apoB-100 and apoB-48.
• Elucidation of apoB-100 primary structure and identification of apoB-48 as a product of RNA-edited apoB mRNA.
• Demonstration that MTP is essential for apoB production and that the proteasome-ubiquitin pathway mediates apoB-100 intracellular degradation.

Conclusions:

• ApoB research has progressed significantly due to breakthroughs in structural elucidation and molecular mechanisms.
• RNA editing and intracellular degradation are critical processes influencing apoB metabolism.
• Further research benefits from the established knowledge of apoB structure, function, and expression.