Nucleoporin Phosphorylation Triggered by the Encephalomyocarditis Virus Leader Protein Is Mediated by Mitogen-Activated Protein Kinases

Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase

“…This inhibition happens in infected cells even before the virus begins to replicate (6,26). The cascade involves Erk1/2 and p38 kinases and is absolutely dependent on Ran:L E interactions and also on the dual phosphorylation of L E itself, an activity that is a prerequisite, and not a consequence, of the Nup modifications (7,10,15,16,27). Furthermore, the L E zinc finger motif must remain intact and chelated to the metal for the protein to function (11).…”

“…Ran, a member of the Ras superfamily of GTPases, normally alternates between nuclear GTP-and cytoplasmic GDP-bound conformers, acting as a molecular switch for the coordinated transport of large molecules back and forth through the nuclear pores (4). However, when L binds Ran, the perverted complex recruits and activates a specific cohort of cellular kinases responsible for the L-induced hyperphosphorylation of Phe/Gly-containing nuclear pore proteins (Nups) (5)(6)(7)(8). The consequence is rapid, potent inhibition of active nuclear-cytoplasmic trafficking.…”

Encephalomyocarditis Virus Leader Is Phosphorylated by CK2 and Syk as a Requirement for Subsequent Phosphorylation of Cellular Nucleoporins

“…L E :Ran is the foundation complex through which host kinases are subsequently recruited in poorly understood secondary steps to carry out the actual Nup hyperphosphorylation events. Inhibition of extracellular signalregulated kinase 1 (ERK1)/ERK2 or p38 pathways prevents L E activities during EMCV-R infection, identifying these kinases as participants if not as the actual phosphate contributors (20).…”

The Leader Protein of Cardioviruses Inhibits Stress Granule Assembly

“…Disruption of the host immune response is critical for the establishment of viral persistence, and the L protein of the virus plays a crucial role in this process. Cardiovirus L proteins are closely related multifunctional proteins shown to interfere with critical cellular processes such as interferon (IFN) and chemokine production (16,32), nucleocytoplasmic trafficking (4,8,17,27,30), apoptosis (12,31), and mitogen-activated protein (MAP) kinase activity (28). Cardiovirus L proteins are very small proteins (about 70 amino acids) in which several domains have been described ( Fig.…”