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- Title
DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2.
- Authors
Fatti, Edoardo; Hirth, Alexander; Švorinić, Andrea; Günther, Matthias; Stier, Gunter; Cruciat, Cristina-Maria; Acebrón, Sergio P.; Papageorgiou, Dimitris; Sinning, Irmgard; Krijgsveld, Jeroen; Höfer, Thomas; Niehrs, Christof
- Abstract
DDX RNA helicases promote RNA processing, but DDX3X also activates casein kinase 1 (CK1ε). We show that other DDX proteins also stimulate the protein kinase activity of CK1ε and that this extends to casein kinase 2 (CK2). CK2 enzymatic activity was stimulated by various DDX proteins at high substrate concentrations. DDX1, DDX24, DDX41, and DDX54 were required for full kinase activity in vitro and in Xenopus embryos. Mutational analysis of DDX3X indicated that CK1 and CK2 kinase stimulation engages its RNA binding but not catalytic motifs. Mathematical modeling of enzyme kinetics and stopped-flow spectroscopy showed that DDX proteins function as nucleotide exchange factors toward CK2 and reduce unproductive reaction intermediates and substrate inhibition. Our study reveals protein kinase stimulation by nucleotide exchange as important for kinase regulation and as a generic function of DDX proteins. From RNA to phosphorylation: RNA helicases promote RNA processing and are important for rearranging RNA structures to promote RNA-protein interactions in an ATP-dependent manner. Fatti et al. showed that DDX RNA helicases could activate the protein kinase CK2, in addition to the previously characterized CK1ε. Their study of the structure and function of DDX3X showed that kinase stimulation occurs through the helicase core domain and that DDX proteins functioned as nucleotide exchange factors to limit undesirable reaction intermediates. This work demonstrates the conserved action of RNA helicases in activating different families of protein kinases and has implications for linking RNA processing to cellular signaling. —AEB
- Subjects
NUCLEOTIDE exchange factors; PROTEIN kinase CK2; HELICASES; ENZYME kinetics; DNA helicases; CASEIN kinase; RNA
- Publication
Science Signaling, 2023, Vol 16, Issue 782, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.abp8923