articleProceedings of the National Academy of SciencesJul 26, 2004GREEN OA

Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells

KMKrishna M. VattemRCRonald C. Wek

Indiana University School of Medicine · Indiana University – Purdue University Indianapolis

PubMed
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Abstract

During cellular stresses, phosphorylation of eukaryotic initiation factor-2 (eIF2) elicits gene expression designed to ameliorate the underlying cellular disturbance. Central to this stress response is the transcriptional regulator activating transcription factor, ATF4. Here we describe the mechanism regulating ATF4 expression involving the differential contribution of two upstream ORFs (uORFs) in the 5' leader of the mouse ATF4 mRNA. The 5' proximal uORF1 is a positive-acting element that facilitates ribosome scanning and reinitiation at downstream coding regions in the ATF4 mRNA. When eIF2-GTP is abundant in nonstressed cells, ribosomes scanning downstream of uORF1 reinitiate at the next coding region,…

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Topics & keywords

Topics
Keywords
  • ATF4
  • Integrated stress response
  • Biology
  • Cell biology
  • eIF2
  • Ribosome
  • Eukaryotic translation
  • Translation (biology)
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