A new double-stranded RNA-binding protein that interacts with PKR
AUTOR(ES)
Coolidge, Candace J.
FONTE
Oxford University Press
RESUMO
We have identified a 74 kDa double-stranded (ds)RNA-binding protein that shares extensive homology with the mouse spermatid perinuclear RNA-binding (Spnr) protein. p74 contains two dsRNA-binding motifs (dsRBMs) that are essential for preferential binding to dsRNA. Previously, dsRNA-binding proteins were shown to undergo homo- and heterodimerization, raising the possibility that regulation of activity could be controlled by interactions between different family members. Homodimerization is required to activate the dsRNA-dependent protein kinase PKR, whereas heterodimerization between PKR and other dsRNA-binding proteins can inhibit kinase activity. We have found that p74 also interacts with PKR, both the wild-type enzyme and a catalytically defective mutant (K296R). While co-expression of p74 and wild-type PKR in the yeast Saccharomyces cerevisiae did not alter PKR activity, co-expression of p74 and the catalytically defective K296R mutant surprisingly resulted in abnormal morphology and cell death in transformants that maintained a high level of p74 expression. These transformants could be rescued by overexpression of the α-subunit of wild-type eukaryotic translation initiation factor 2 (eIF2α), one of the known substrates for PKR. We hypothesize that competing heterodimers between p74–K296R PKR and eIF2α–K296R PKR may control cell growth such that stabilization of the p74–K296R PKR heterodimer induces abnormal morphology and cell death.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=111047Documentos Relacionados
- A conserved double-stranded RNA-binding domain.
- Straightening of bulged RNA by the double-stranded RNA-binding domain from the protein kinase PKR
- RNA recognition by a Staufen double-stranded RNA-binding domain
- Chimeric double-stranded RNA-specific adenosine deaminase ADAR1 proteins reveal functional selectivity of double-stranded RNA-binding domains from ADAR1 and protein kinase PKR
- The double-stranded RNA-binding protein X1rbpa promotes RNA strand annealing.
