4.7 Article

Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability

Journal

Publisher

MDPI
DOI: 10.3390/ijms24076067

Keywords

hypusine; EIF5AL1; protein stability; migration; proliferation

Ask authors/readers for more resources

The EIF5A family consists of EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that EIF5As are involved in various human diseases. EIF5A1 can act as a tumor suppressor or oncogene in different cancers, while EIF5A2 promotes cancer development. EIF5AL1's biological function has not been studied, but it has been found to inhibit cell proliferation and migration. The differences in hypusination and protein turnover between EIF5A1 and EIF5AL1 may explain their differential protein expression levels. This research fills gaps in EIF5As research and provides insights for future studies on EIF5AL1.
The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available