Take our Survey

Reference: Pereira CM, et al. (2005) IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1 and inhibits GCN2 activation. J Biol Chem 280(31):28316-23

Reference Help

Abstract


Translational control directed by the eIF2alpha kinase GCN2 is important for coordinating gene expression programs in response to nutritional deprivation. The GCN2 stress response is conserved from yeast to mammals and is critical for resistance to nutritional deficiencies and for the control of feeding behaviors in rodents. IMPACT, a mouse imprinted gene, has sequence similarities with the yeast YIH1 protein, an inhibitor of GCN2. YIH1 competes with GCN2 for binding to a positive regulator, GCN1. In this work, we present evidence that IMPACT is the functional counterpart of YIH1. Overexpression of IMPACT in yeast lowers both basal and amino acid starvation-induced levels of phosphorylated eIF2alpha, as previously described for YIH1. Overexpression of IMPACT in mouse embryonic fibroblasts inhibits phosphorylation of eIF2alpha by GCN2 under leucine starvation, abolishing expression of its downstream target genes, ATF4(CREB-2) and CHOP(GADD153). IMPACT binds to the minimal yeast GCN1 segment required for the interaction with yeast GCN2 and YIH1, and to mouse native GCN1. At the protein level, IMPACT was detected mainly in the brain. IMPACT is abundant in the majority of hypothalamic neurons. Scattered neurons expressing this protein at higher levels were detected in other regions, such as the hippocampus and the piriform cortex. The abundance of IMPACT is inversely correlated with eIF2alpha(P) levels in different brain areas. These results taken together thus suggest that IMPACT ensures constant high levels of translation and low levels of ATF4 and CHOP in specific neuronal cells under amino acid starvation conditions.

Reference Type
Journal Article
Authors
Pereira CM, Sattlegger E, Jiang HY, Longo BM, Jaqueta CB, Hinnebusch AG, Wek RC, Mello LE, Castilho BA
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference