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.

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.

Recent insights into eukaryotic translation initiation factors 5A1 and 5A2 and their roles in human health and disease.

The eukaryotic translation initiation factor 5A1 (eIF5A1) and its homolog eIF5A2 are the only two human proteins containing the unique post-translational modification-hypusination, which is essential for the function of these two proteins. eIF5A1 was initially identified as a translation initiation factor by promoting the first peptide bond formation of protein during translation; however, recent results suggest that eIF5A1 also functions as a translation elongation factor. It has been shown that eIF5A1 is implicated in certain human diseases, including diabetes, several human cancer types, viral infections and diseases of neural system. Meanwhile, eIF5A2 is overexpressed in many cancers, and plays an important role in the development and progression of cancers. As multiple roles of these two factors were observed among these studies, therefore, it remains unclear whether they act as oncogene or tumor suppressor. In this review, the recent literature of eIF5As and their roles in human diseases, especially in human cancers, will be discussed.

The Impact of Coilin Nonsynonymous SNP Variants E121K and V145I on Cell Growth and Cajal Body Formation: The First Characterization.

Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene (COIL) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.