Biochimica et Biophysica Acta 2015-07-01

Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127.

Christian Borgo, Cinzia Franchin, Valentina Salizzato, Luca Cesaro, Giorgio Arrigoni, Laura Matricardi, Lorenzo A Pinna, Arianna Donella-Deana

Index: Biochim. Biophys. Acta 1853 , 1693-701, (2015)

Full Text: HTML

Abstract

In eukaryotic protein synthesis the translation initiation factor 3 (eIF3) is a key player in the recruitment and assembly of the translation initiation machinery. Mammalian eIF3 consists of 13 subunits, including the loosely associated eIF3j subunit that plays a stabilizing role in the eIF3 complex formation and interaction with the 40S ribosomal subunit. By means of both co-immunoprecipitation and mass spectrometry analyses we demonstrate that the protein kinase CK2 interacts with and phosphorylates eIF3j at Ser127. Inhibition of CK2 activity by CX-4945 or down-regulation of the expression of CK2 catalytic subunit by siRNA cause the dissociation of j-subunit from the eIF3 complex as judged from glycerol gradient sedimentation. This finding proves that CK2-phosphorylation of eIF3j is a prerequisite for its association with the eIF3 complex. Expression of Ser127Ala-eIF3j mutant impairs both the interaction of mutated j-subunit with the other eIF3 subunits and the overall protein synthesis. Taken together our data demonstrate that CK2-phosphorylation of eIF3j at Ser127 promotes the assembly of the eIF3 complex, a crucial step in the activation of the translation initiation machinery. Copyright © 2015 Elsevier B.V. All rights reserved.