Translation inhibition in apoptosis - Caspase-dependent PKR activation and eIF2-alpha phosphorylation
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Saelens, X; Kalai, M; Vandenabeele, P
Abstract
The protein kinase PKR is a major player in the cellular antiviral response, acting mainly by phosphorylation of the alpha -subunit of the eukaryotic translation initiation factor 2 (eIF2-alpha) to block de novo protein synthesis. PKR activation requires binding of double-stranded RNA or PACT/RAX proteins to its regulatory domain. Since several reports have demonstrated that translation is inhibited in apoptosis, we investigated whether PKR and eIF2-alpha phosphorylation contribute to this process. We show that PKR is proteolysed and that eIF2-alpha is phosphorylated at the early stages of apoptosis induced by various stimuli. Both events coincide with the onset of caspase activity and are prevented by caspase inhibitors. Using site-directed mutagenesis we show that PKR is specifically proteolysed at Asp(251) during cellular apoptosis. This site is cleaved in vitro by recombinant caspase-3, caspase-7, and caspase-8 and not by the proinflammatory caspase-1 and caspase-11. The released kinase domain efficiently phosphorylates eIF2-alpha at the cognate Ser(51) residue, and its overexpression in mammalian cells impairs the translation of its own mRNA and of reporter mRNAs. Our results demonstrate a new and caspase-dependent activation mode for PKR, leading to eIF2-alpha phosphorylation and translation inhibition in apoptosis.
Radio Aurora Explorer: A Mission Overview
JOURNAL OF SPACECRAFT AND ROCKETS
Authors: Cutler, James W.; Bahcivan, Hasan
Abstract
The primary objective of the Radio Aurora Explorer mission is to study plasma instabilities that lead to magnetic field aligned irregularities of electron density in the lower polar ionosphere (80-400 km). These irregularities are known to disrupt communication and navigation signals. The Radio Aurora Explorer mission uses a bistatic radar configuration; the spacecraft is the radar receiver and the transmitters are several worldwide incoherent scatter radars of which the primary radar is located in Poker Flat, Alaska. The satellites are 3 kg, university-class CubeSats with a primary payload of a direct-conversion radar receiver operating in the frequency range from 426 to 510 MHz. The satellite bus has a novel configuration of processing, attitude control, and antenna design that met the physical constraints of the CubeSat form factor and the one-year schedule constraint imposed by launch dates. Two satellites have launched: RAX-1 on 19 November 2010 onboard a Minotaur-IV rocket from Kodiak, Alaska, and RAX-2 on 28 October 2011 onboard a Delta-II rocket from Vandenberg U.S. Air Force Base, California. RAX-2 has detected and measured irregularities during multiple experiments over Alaska and Canada. Preliminary analysis indicates unprecedented characterization of the irregularities.