Anti-eIF4G1 (aa96-600) monoclonal antibody, clone 5HS22

Eukaryotic ribosomes contain the high-affinity protein kinase C beta II (PKC beta II) scaffold, receptor for activated C kinase (RACK1), but its role in protein synthesis control remains unclear. We found that RACK1: PKC beta II phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at S1093 and eIF3a at S1364. We showed that reversible eIF4G(S1093) phosphorylation is involved in a global protein synthesis surge upon PKC-Raf-extracellular signal-regulated kinase 1/2 (ERK1/2) activation and in induction of phorbol ester-responsive transcripts, such as cyclooxygenase 2 (Cox-2) and cyclin-dependent kinase inhibitor (p21(Cip1)), or in 5' 7-methylguanosine (m(7)G) cap-independent enterovirus translation. Comparison of mRNA and protein levels revealed that eIF4G1 or RACK1 depletion blocked phorbol ester-induced Cox-2 or p21Cip1 expression mostly at the translational level, whereas PKC beta inhibition reduced them both at the translational and transcript levels. Our findings reveal a physiological role for ribosomal RACK1 in providing the molecular scaffold for PKC beta II and its role in coordinating the translational response to PKC-Raf-ERK1/2 activation.

The Asp620Asn mutation in the vacuolar protein sorting protein 35 (VPS35) gene and the Arg1205His mutation in the eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) gene were identified in autosomal dominant late-onset familial and sporadic Parkinson disease (PD) patients in a Caucasian population. However, the frequencies of these 2 mutations among Chinese PD patients are unknown. We examined these mutations in a large cohort consisting of 609 PD patients and 600 healthy control subjects from Southwest China. Our results suggest that the Asp620Asn mutation in VPS35 and the Arg1205His mutation in EIF4G1 do not play a role in PD in the Southwest China population. The novel Arg1205Cys mutation in EIF4G1 detected in the current study should be further studied among other Asian patients. (C) 2013 Elsevier Inc. All rights reserved.