Perk is essential for translational regulation and cell survival during the unfolded protein response.

By H. Harding, Yuhong Zhang, A. Bertolotti, Huiqing Zeng, D. Ron. Molecules and Cells, 2000

2,019 citations recorded by the source corpus.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3c797163e791540edb3a32afa7e06f919b7d00b5

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. D. Ron
4. J. Malhotra
5. C. Hetz
6. Peter Walter
7. H. Harding
8. M. Schröder

In Epidemiology

1. R. Kaufman
2. G. Hotamışlıgil
3. J. Malhotra
4. D. Ron
5. Guido Kroemer
6. C. Hetz
7. Peter Walter
8. Afshin Samali

In Molecular Biology

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

Citations in the corpus

• The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages (2003, background): “Induction of CHOP in the UPR is dependent on activation of the endoplasmic-reticulum-resident protein kinase, PERK, which induces the upstream transcription factor ATF-4 (ref”
• Translational control in stress and apoptosis (2005, background): “Remarkably, the stress-induced attenuation of global translation is often accompanied by a switch to the selective translation of proteins that are required for cell survival under stres”
• The unfolded protein response in nutrient sensing and differentiation (2002, background): “In cultured cells, PERK-mediated phosphorylation of eIF2α was require”
• Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. (2001, methodology): “…the UPR in single worms. cantly reduced both in Perk null cells and in cells bearing a homozygous Ser51→Ala mutation (S51A) in the eIF2 RNA Interference Shows that Either ire-1 gene to prevent phosphorylation (Harding et al., 2000; or pek-1 Is Required for Larval Development Scheuner et al., 2001).”
• ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. (2004, background): “All antibodies tested were purchasedet al., 2000; Harding et al., 2000; Zhang et al., 2002). from Santa Cruz except ATF4-N which was raised against epitopeHowever, PERK deficiency affects other secretory cells QETNKEPPQTVNPIGHLPES.”
• Regulated Ire1-dependent decay of messenger RNAs in mammalian cells (2009, background): “In contrast, conditions such as viral infection may call for a more destructive response that limits the load of incoming proteins, which is analogous to the effects of reduced translation mediated by the PERK (PKR-like ER kinase) branch of the UPR (Harding et al., 2000).”
• CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. (2004, methodology): “The importance of the UPR to secretory cell homeostasis is re- vealed by the phenotype of mutations affecting UPR signaling; these are associated with enhanced cell death and with defective secretory capacity (Harding et al. 2000b, 2001; Scheuner et al. 2001; Shen et al. 2001; Zhang et al. 2002).”
• Mediators of endoplasmic reticulum stress‐induced apoptosis (2006, background): “Inhibition of translation with cycloheximide reduced ER stress-induced cell death, confirming that blocking the accumulation of unfolded nascent proteins is crucial for cell survival (Harding et al, 2000).”
• The endoplasmic reticulum and the unfolded protein response. (2007, background): “These transducers are two protein kinases IRE1 (inositol requiring kinase 1) [8,9], and PERK (double stranded RNA-activated protein kinase-like ER kinase) [10] and the transcription factor ATF6 (activating transcription factor 6) [9,11].”
• ATF6 Activated by Proteolysis Binds in the Presence of NF-Y (CBF) Directly to the cis-Acting Element Responsible for the Mammalian Unfolded Protein Response (2000, background): “It has recently been shown that the ER-resident transmembrane protein kinase PERK (also known as PEK) plays a major role in ER stress-induced translational attenuation (16, 17, 47).”
• The impact of the unfolded protein response on human disease (2012, background): “The PERK–eIF2 arm of the UPR is indispensable for  cells to adapt to large fluctuations in proinsulin synthesis (Harding et al., 2000b; Scheuner et al., 2001).”
• The integrated stress response (2016, positive): “…pathway, PERK, which phosphorylates eIF2 a to activate the ISR, functions in concert with the other arms of the UPR, IRE1, and ATF6, to ameliorate proteotoxicity by enhancing the transcription of genes that promote protein folding and degradation of misfolded or aggregated polypeptides [175,176].”