RT Journal Article
T1 Activation of the double-stranded RNA-dependent protein kinase PKR by small ubiquitin-like modifier (SUMO).
A1 de la Cruz-Herrera, Carlos F
A1 Campagna, Michela
A1 García, Maria A
A1 Marcos-Villar, Laura
A1 Lang, Valerie
A1 Baz-Martínez, Maite
A1 Gutiérrez, Sylvia
A1 Vidal, Anxo
A1 Rodríguez, Manuel S
A1 Esteban, Mariano
A1 Rivas, Carmen
K1 Double-stranded RNA (dsRNA)
K1 Protein Kinase RNA-activated (PKR)
K1 Sumoylation
K1 Translation Control
K1 Virus
K1 Activación enzimática
K1 Interacciones huésped-patógeno
K1 Inmunidad innata
K1 Mapeo peptídico
K1 Unión proteica
K1 ARN bicatenario
K1 ARN viral
K1 Proteína SUMO-1
K1 Análisis de secuencia de proteína
K1 Sumoilación
K1 Replicación viral
K1 eIF-2 quinasa
K1 Células 3T3
K1 Animales
K1 Multimerización de proteínas
K1 Ratones
AB The dsRNA-dependent kinase PKR is an interferon-inducible protein with ability to phosphorylate the α subunit of the eukaryotic initiation factor (eIF)-2 complex, resulting in a shut-off of general translation, induction of apoptosis, and inhibition of virus replication. Here we analyzed the modification of PKR by the small ubiquitin-like modifiers SUMO1 and SUMO2 and evaluated the consequences of PKR SUMOylation. Our results indicate that PKR is modified by both SUMO1 and SUMO2, in vitro and in vivo. We identified lysine residues Lys-60, Lys-150, and Lys-440 as SUMOylation sites in PKR. We show that SUMO is required for efficient PKR-dsRNA binding, PKR dimerization, and eIF2α phosphorylation. Furthermore, we demonstrate that SUMO potentiates the inhibition of protein synthesis induced by PKR in response to dsRNA, whereas a PKR SUMOylation mutant is impaired in its ability to inhibit protein synthesis and shows reduced capability to control vesicular stomatitis virus replication and to induce apoptosis in response to vesicular stomatitis virus infection. In summary, our data demonstrate the important role of SUMO in processes mediated by the activation of PKR.
PB American Society for Biochemistry and Molecular Biology
SN 0021-9258
YR 2014
FD 2014-09-19
LK http://hdl.handle.net/10668/2245
UL http://hdl.handle.net/10668/2245
LA en
NO de la Cruz-Herrera CF, Campagna M, García MA, Marcos-Villar L, Lang V, Baz-Martínez M, et al. Activation of the double-stranded RNA-dependent protein kinase PKR by small ubiquitin-like modifier (SUMO). J. Biol. Chem.. 2014                         ; 289(38):26357-67
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 11, 2025