DESCRIPTION:

Genes downregulated in livers of Eif2ak3(Perk)-mutant mice 30 minutes after perfusion witht tBuHQ. tBuHQ is used to generate ER-stress. Sequences reported in the manuscript were used to search the Mouse Genome Informatics (MGI) resource using the batch query form on June 22, 2018. Sequences that did not match were investigated manually. In some cases, sequence identifiers were identified by cross-referencing the array data in the Gene Expression Omnibus. Sequences that were associated with putative assignments to gene identifiers via a 'probe' relationship in MGI were included. Values represent z-scores. Higher scores were used for genes represented more than once.

LABEL:

Down in Eif2ak3 with tBuHQ

SCORE TYPE:

Effect

DATE ADDED:

2018-07-18

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Dang Do AN, Kimball SR, Cavener DR, Jefferson LS

TITLE:

eIF2alpha kinases GCN2 and PERK modulate transcription and translation of distinct sets of mRNAs in mouse liver.

JOURNAL:

Physiological genomics Aug 2009, Vol 38, pp. 328-41

ABSTRACT:

In eukaryotes, selective derepression of mRNA translation through altered utilization of upstream open reading frames (uORF) or internal ribosomal entry sites (IRES) regulatory motifs following exposure to stress is regulated at the initiation stage through the increased phosphorylation of eukaryotic initiation factor 2 on its alpha-subunit (eIF2alpha). While there is only one known eIF2alpha kinase in yeast, general control nonderepressible 2 (GCN2), mammals have evolved to express at least four: GCN2, heme-regulated inhibitor kinase (HRI), double-stranded RNA-activated protein kinase (PKR), and PKR-like endoplasmic reticulum-resident kinase (PERK). So far, the main known distinction among these four kinases is their activation in response to different acute stressors. In the present study, we used the in situ perfused mouse liver model and hybridization array analyses to assess the general translational response to stress regulated by two of these kinases, GCN2 and PERK, and to differentiate between the downstream effects of activating GCN2 versus PERK. The resulting data showed that at least 2.5% of mouse liver mRNAs are subject to derepressed translation following stress. In addition, the data demonstrated that eIF2alpha kinases GCN2 and PERK differentially regulate mRNA transcription and translation, which in the latter case suggests that increased eIF2alpha phosphorylation is not sufficient for derepression of translation. These findings open an avenue for more focused future research toward groups of mRNAs that code for the early cellular stress response proteins. PUBMED: 19509078
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