Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A)

Area of Science:

• Molecular Biology
• Cell Biology
• Protein Biochemistry

Background:

• Eukaryotic translation initiation factor 5A (eIF5A) is crucial for protein synthesis.
• eIF5A requires hypusination for its function, a modification it also undergoes acetylation.
• The functional role of eIF5A acetylation remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of eIF5A acetylation in regulating its cellular function.
• To identify the enzymes responsible for eIF5A acetylation and deacetylation.
• To determine how acetylation impacts eIF5A's subcellular localization.

Main Methods:

• Identification of eIF5A acetyltransferase using in vitro assays.
• Characterization of eIF5A deacetylases through enzymatic assays.
• Analysis of eIF5A subcellular localization under conditions of altered acetylation or hypusination.

Main Results:

• PCAF was identified as the primary acetyltransferase for eIF5A.
• HDAC6 and SIRT2 were identified as the major deacetylases for eIF5A.
• Inhibition of deacetylases or impaired hypusination led to eIF5A acetylation and nuclear accumulation.

Conclusions:

• Acetylation dynamically regulates the subcellular localization of eIF5A.
• Reversible acetylation, alongside constitutive hypusination, plays a key role in controlling eIF5A's cellular distribution.
• This provides a novel regulatory mechanism for eIF5A function in eukaryotic translation.