Distinct Induction Patterns and Functions of Two Closely Related Interferon-inducible Human Genes, ISG54 and ISG56

Fulvia Terenzi,Daniel J Hui,William C Merrick,Ganes C Sen

doi:10.1074/jbc.m605771200

Fulvia Terenzi, Daniel J Hui + Show 2 more

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https://doi.org/10.1074/jbc.m605771200

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Abstract

Human P54 and P56 proteins are tetratricopeptide proteins that are encoded by two closely related genes, ISG54 and ISG56. These genes are induced strongly but transiently when cells are treated with interferons or double-stranded RNA or infected with a variety of viruses. We observed that, although double-stranded RNA or Sendai virus infection induced the two genes with similar kinetics, their induction kinetics in response to interferon-beta were quite different. The induction kinetics by virus infection were also different between two cell lines. Functionally the two proteins were similar. Like P56, P54 bound to the translation initiation factor eIF3 and inhibited translation. However, unlike P56, P54 bound to both the "e" and the "c" subunits of eIF3. Consequently, P54 inhibited two functions of eIF3. Like P56, it inhibited the ability of eIF3 to stabilize the eIF2 x GTP x Met-tRNA(i) ternary complex. But in addition, it also inhibited the formation of the 48 S pre-initiation complex between the 40 S ribosomal subunit and the 20 S complex composed of eIF3, ternary complex, eIF4F, and mRNA. Thus, although similar in structure, the human P54 and P56 proteins are induced differently and function differently.

Highlights

On the same cis-element in their promoters, the IFN-stimulated response elements (8 –11)
ISG56 and ISG54 Are Induced Differently—The kinetics of transcriptional induction of the human ISG56 and ISG54 genes in response to IFN-␤ treatment of HT1080 cells were measured using a quantitative RNase protection assay for the two mRNAs; actin mRNA served as the internal control (Fig. 1)
There were no detectable levels of the ISG56 and the ISG54 mRNAs in untreated cells; both mRNAs were induced strongly by IFN-␤ treatment for 6 h, ISG56 mRNA was induced to a higher level

Summary

Introduction

On the same cis-element in their promoters, the IFN-stimulated response elements (8 –11). The mouse proteins, on the other hand, bind to eIF3c and block the ability of eIF3 to promote formation of the 48 S pre-initiation complex containing Induction and Functions of ISG54 and ISG56 the 40 S ribosomal subunit, the ternary complex, eIF4F, and mRNA [41].

Results

Conclusion