Regulated translation initiation controls stress-induced gene expression in mammalian cells.

By H. Harding, I. Novoa, Yuhong Zhang, Huiqing Zeng, R. Wek, M. Schapira, D. Ron. Molecules and Cells, 2000

3,269 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dc7840258acbb926e2121dbb577f28b6ccdeddf1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. R. Kaufman
2. G. Hotamışlıgil
3. C. Hetz
4. D. Ron
5. J. Malhotra
6. Laurie H. Glimcher
7. M. Schröder
8. Peter Walter

In Molecular Biology

1. R. Kaufman
2. G. Hotamışlıgil
3. D. Ron
4. C. Hetz
5. J. Malhotra
6. M. Schröder
7. H. Harding
8. Laurie H. Glimcher

Citations in the corpus

• The unfolded protein response in nutrient sensing and differentiation (2002, background): “pl?P18848"> ATF4 mRNA requires phosphorylation of eIF2α in a manner that requires ORFs in the 5′ UTR of the mRN”
• The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. (2010, background): “ATF4 expression is induced due to its selective translation during hypoxia, which is mediated by upstream ORFs in its 5′UTR, whereas CHOP is at least partially transcriptionally induced by ATF4 (42).”
• Translational control in the endoplasmic reticulum stress response. (2002, background): “For example, PKR, which is activated by doublestranded RNA, phosphorylates eIF2α during viral infection (10), and GCN2 and HRI play the equivalent role in amino acid–starved cells and heme-deprived reticulocytes, respectively (8, 11, 12).”
• The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae (2012, background): “In yeast and mammalian cells, this is achieved by phosphorylation of eIF2a at a conserved serine (Ser51) residue (Pavitt et al. 1998; Harding et al. 2000).”
• Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities (2008, background): “Interestingly PERK −/− and AFT4 −/− cells and EIF2α (Ser51Ala) knock-in cells fail to induce CHOP during ER stres”
• Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword? (2007, positive): “Analysis of Sil1 mutant mice demonstrated that affected Purkinje cells have ubiquitinated nuclear-and ER-associated protein aggregates and also display upregulation of several ER stress markers (BiP, CHOP, and ORP150) (166).”
• An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. (2003, methodology): “GCN2 activates Atf4 in mammalian cells Likewise, mouse fibroblasts lacking Atf4 are unable to (Harding et al., 2000a), which may explain the limited grow in culture unless provided supplemental amino impact of Perk deletion on the mammalian Atf4-depenacids.”
• Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes (2012, positive): “It phosphorylates eIF2a [116], thereby regulating insulin translation [117].”
• Endoplasmic reticulum stress sensing in the unfolded protein response. (2013, background): “One such mRNA encodes the transcription factor ATF4 that activates downstream UPR target genes, including GADD34 (growth arrest and DNA damage-inducible 34) and CHOP (transcription factor C/ EBP homologous protein) (Harding et al. 2000; Scheuner et al. 2001).”
• Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. (2011, background): “The different pathways are regulated by the three sensors ATF6 (activating transcription factor 6 alpha), IRE1 (inositol requiring 1), and PERK (PKR like ER kinase).”
• Nutrient sensing and TOR signaling in yeast and mammals (2017, neutral): “The uORF containing mRNA encodes a basic leucine zipper transcription factor termed ATF4 (activating transcription factor 4) in mammals (Harding et al , 2000; Vattem & Wek, 2004) and Gcn4 in yeast (Hinnebusch, 1984).”
• The endoplasmic reticulum stress response in immunity and autoimmunity (2008, background): “PERK also phosphorylates and inactivates eukaryotic translation-initiation factor 2α ( EIF2α ; also known as EIF2S1), thereby arresting most mRNA translation to alleviate additional sources of ER stres”
• Coupling endoplasmic reticulum stress to the cell death program (2004, background): “subsequently activated by p38 mitogen-associated protein kinase.(1,7,63,120) Several reports suggest that CHOP negatively regulates cell growth and promotes ER stress-induced apoptosis.”