Translation of Atf4

Stable Identifier
R-MMU-9635380
Type
Reaction [omitted]
Species
Mus musculus
Compartment
cytosol, nucleoplasm
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Translation of Atf4
Atf4 mRNA is translated to yield Atf4 protein, which then transits to the nucleus (Harding et al. 2000, Lu et al. 2004, Vattem and Wek 2004, Dey et al. 2010). Phosphorylation of Eif2s1 (eIF2-alpha) causes increased translation of Atf4 mRNA (Harding et al. 2000, Lu et al. 2004, Vattem and Wek 2004, Dey et al. 2010, Zhang et al. 2018, Zhang et al. 2019). The mRNA of Atf4 contains 2 upstream ORFs (uORFs) (Vattem and Wek 2004). The second uORF overlaps the ORF encoding ATF4 and thus prevents translation of Atf4. When Eif2s1 (eIF2-alpha) is phosphorylated, translation of the uORFs is suppressed and translation of the ORF encoding Atf4 is increased (Harding et al. 2000, Lu et al. 2004, Vattem and Wek 2004, Dey et al. 2010, Zhang et al. 2018, Zhang et al. 2019).
Literature References
PubMed ID Title Journal Year
29101239 HRI coordinates translation by eIF2αP and mTORC1 to mitigate ineffective erythropoiesis in mice during iron deficiency

Kaufman, RJ, Macias-Garcia, A, Paltrinieri, E, Zhang, S, Velazquez, J, Chen, JJ

Blood 2018
15277680 Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells

Wek, RC, Vattem, KM

Proc Natl Acad Sci U S A 2004
15479734 Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response

Ron, D, Lu, PD, Harding, HP

J Cell Biol 2004
31033440 HRI coordinates translation necessary for protein homeostasis and mitochondrial function in erythropoiesis

Macias-Garcia, A, Zhang, S, Butty, VL, Levine, SS, Sankaran, VG, Velazquez, J, Ulirsch, JC, Chen, JJ

Elife 2019
20732869 Both transcriptional regulation and translational control of ATF4 are central to the integrated stress response

Zhou, D, Dey, S, Wek, RC, Palam, LR, Baird, TD, Spandau, DF

J. Biol. Chem. 2010
11106749 Regulated translation initiation controls stress-induced gene expression in mammalian cells

Zhang, Y, Harding, HP, Schapira, M, Wek, R, Zeng, H, Ron, D, Novoa, I

Mol. Cell 2000
Participants
Input
Output
This event is regulated
Positively by
Regulator
p-S52-Eif2s1:Eif2s2:Eif2s3 [cytosol] (Mus musculus)
Orthologous Events
Translation of ATF4 (Homo sapiens)
Authored
May, B  (2019-02-03)
Reviewed
Staschke, KA  (2019-11-20)
Chen, JJ  (2019-10-22)
Bruhat, A  (2019-09-15)
Urano, F  (2010-04-30)
Created
May, B  (2019-02-03)
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