Memory versus Starvation: What can yeast tell us about Yihl mediated regulation of protein kinase Gcn2?

摘要

How do cells endure/overcome environmental or intracellular stresses? In all eukaryotes, one major mechanism is to adjust protein synthesis via phosphorylating translation factor eIF2α. The eIF2α kinase Gcn2 is essential for overcoming amino acid hunger. For sensing starvation, the Gcn2 RWD domain must directly bind to its effector protein Gcn1. Curiously, Gcn2 is also required for long term memory formation. The mammalian protein IMPACT, highly expressed in neurons, and its yeast ortholog Yih1, consist of an Ancient Domain and an RWD domain with Gcn1 binding activity. Yih1/IMPACT competes with Gcn2 for Gcn1 binding thereby diminishing Gcn2 activity. Yih1 also binds monomeric G-actin, a component of the cytoskeleton. Our studies suggest that Yih1 inhibits Gcn2 when released from G-actin, and only under certain physiological conditions or in specific cellular compartments.