c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies

Abstract

JNK-mediated phosphorylation of the mRNA-decapping protein DCP1a disrupts P body structure, mRNA stability, and gene expression in response to stress and inflammatory stimuli.

mRNP granules

“…52,53 O-linked N-acetyl glucosamine, 53 poly (ADP) ribosylation, 54 acetylation, and ubiqutination 39 are also modifications present on specific stress granule components, which have been implicated in stress granule assembly, albeit the mechanisms are not entirely clear. Finally, the phosphorylation of several proteins, including G3BP, 29 TTP, 55 Dcp1, 42,56 Dcp2, 57 and 4E-T 58 alters their localization within, and/or the assembly of their respective granules. In addition, phosphorylation in the prion-like domain of FUS impairs hydrogel formation in vitro.…”

mRNA Decapping Enzyme 1a (Dcp1a)-induced Translational Arrest through Protein Kinase R (PKR) Activation Requires the N-terminal Enabled Vasodilator-stimulated Protein Homology 1 (EVH1) Domain

“…Dcp1a in P-bodies constantly and quickly exchanges with Dcp1a in the cytoplasmic pool during fluorescence recovery after photobleaching analysis (34). Phosphorylation at Ser-315 mediates Dcp1a release from P-bodies as well as the regulation of P-body formation during translational stress (32), which suggests that Dcp1a may be involved in modulation of, or signal transduction from, P-bodies. In contrast, Dcp2 has a slower recovery rate during fluorescence recovery after photobleaching experiments, suggesting that it is a core P-body protein (34).…”

“…Previous studies have indicated roles for Dcp1a in P-body formation, maintenance, and regulation (6,32,33). Dcp1a in P-bodies constantly and quickly exchanges with Dcp1a in the cytoplasmic pool during fluorescence recovery after photobleaching analysis (34).…”

“…However, the human Dcp1a-Dcp2 interaction is thought to require the cofactors enhancer of decapping 3 and 4 (EDC3 and EDC4) as well as the RNA helicase Rck/p54 (8, 29 -31). Dcp1a and other proteins involved in mRNA degradation or translation repression are key factors in messenger ribonucleoprotein granule assembly (20,32). Conditions that decrease translation rates inside the cell and those that activate mRNA decapping and degradation increase the size and number of P-bodies (4 -6, 19).…”

Viral activation of stress-regulated Rho-GTPase signaling pathway disrupts sites of mRNA degradation to influence cellular gene expression

“…Recent studies have pinpointed phosphorylation of PB resident proteins as key to the control of their assembly. [60][61][62] For example, the direct phosphorylation of PB scaffolding protein Pat1 by cAMP-dependent protein kinase PKA causes PB dissolution and reduces cell survival in times of stress. 60 Similarly, several viruses have been shown to accelerate the decay of PB resident proteins, or recruit PB resident proteins to viral replication compartments to enhance replication.…”