JDP2 is directly regulated by ATF4 and modulates TRAIL sensitivity by suppressing the ATF4–DR5 axis

Engler, Máté János; Mimura, Junsei; Yamazaki, Shun; Itoh, Ken

doi:10.1002/2211-5463.13017

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…JUN dimerisation protein 2 (JDP2) is another bZIP TF identified as an ATF4 target gene and ATF4 dimerisation partner, it has been found to inhibit ATF4 transcriptional activity for some target genes including asparagine synthetase (ASNS; Engler et al, 2020 ). Nuclear factor erythroid-2-like 1 (NFE2L1) is a cap ‘n’ collar bZIP TF found to be a target gene and dimerisation partner of ATF4.…”

Section: Discussionmentioning

confidence: 99%

A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response

Neill

Masson

2023

Front. Mol. Neurosci.

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ATF4 is a cellular stress induced bZIP transcription factor that is a hallmark effector of the integrated stress response. The integrated stress response is triggered by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 complex that can be carried out by the cellular stress responsive kinases; GCN2, PERK, PKR, and HRI. eIF2α phosphorylation downregulates mRNA translation initiation en masse, however ATF4 translation is upregulated. The integrated stress response can output two contradicting outcomes in cells; pro-survival or apoptosis. The mechanism for choice between these outcomes is unknown, however combinations of ATF4 heterodimerisation partners and post-translational modifications have been linked to this regulation. This semi-systematic review article covers ATF4 target genes, heterodimerisation partners and post-translational modifications. Together, this review aims to be a useful resource to elucidate the mechanisms controlling the effects of the integrated stress response. Additional putative roles of the ATF4 protein in cell division and synaptic plasticity are outlined.

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Section: Discussionmentioning

confidence: 99%

A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response

Neill

Masson

2023

Front. Mol. Neurosci.

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“…Downregulation of Map4k2 at 100 μM palmitic acid can inhibit Bcl2l2 through JNK signaling [53]. Jun dimerization protein 2 ( Jdp2 ) is a transcription factor involved in cell survival [54] and was also downregulated at 100 μM palmitic acid.…”

Section: Resultsmentioning

confidence: 99%

Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids

Valencia

Mariño

Noutsos

et al. 2021

Preprint

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Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis are unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show differential effects of low and high concentrations of oleic or palmitic acid treatment on differential gene transcription. Gene ontology analysis uncovered significant gene enrichment in several cellular pathways involved in gene regulation and protein production, particularly with proliferation, migration, and cell survival. The enriched signaling pathways include Wnt, integrin, PDGF, and apoptosis, in addition endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration show low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduced hypothalamic neuronal migration, with little effects by palmitic acid. The results show direct impact of the two most abundant fatty acids in a high fat diet to directly impact hypothalamic neuronal proliferation and migration. The results also uncovered signaling pathways affected by oleic and palmitic acid and suggest a mechanism of prenatal high-fat diet induced neurogenesis events is through these two abundant fatty acids.

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“…Knockdown of JDP2 enhanced the expression of ATF4 target genes, including DR4 and DR5 in HeLa cells. Whereas, overexpression of JDP2 repressed ER stress-mediated transcriptional activation of DR5 which clearly suggested that JDP2 caused negative regulation of ATF4-mediated gene expression (21).…”

Section: Recent Breakthroughs In Trail-driven Signaling: Fresh From T...mentioning

confidence: 97%

“…JDP2 (Jun dimerization protein 2) is a bZip type transcriptional factor (21). Knockdown of JDP2 enhanced the expression of ATF4 target genes, including DR4 and DR5 in HeLa cells.…”

Section: Recent Breakthroughs In Trail-driven Signaling: Fresh From T...mentioning

confidence: 99%

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

Farooqi

Naureen

Yılmaz

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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Cancer is a therapeutically challenging disease because of its heterogeneous and multifaceted nature. Decades of research have sequentially and systematically enabled us to develop a sharper and better understanding of the heterogeneous nature of cancer. Genetic, genomic and proteomic studies have unraveled wide-ranging signaling cascades which play cornerstone role in disease onset and progression. More importantly, activation of pro-survival signaling and loss of apoptosis also play critical role in cancer progression. TRAIL-mediated signaling pathway has emerged as one of the most comprehensively analyzed cascade because of its exceptional ability to target cancer cells while leaving normal cells intact. TRAIL discovery and landmark achievements related to TRAIL/TRAIL-receptor signaling pathway attracted the attention of researchers. Therefore, scientists started to add missing pieces to an incomplete jig-saw puzzle and allowed contemporary researchers to conceptualize a better molecular snapshot of TRAIL-induced signaling in various cancers. Circumstantial evidence illuminated a functionally unique "push and pull" between anti-apoptotic and pro-apoptotic proteins in different cancers. Overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins shifted the balance towards loss of apoptosis. There has been a breakneck increase in the number of clinical trials related to TRAIL-based therapeutics which validate the true pharmacological potential of TRAIL-based therapeutics as effective anticancer agents. However, apart from advancements in our clinical understanding about the efficacy of TRAIL-based therapeutics, researchers have also faced setbacks in the field of translational medicine. Therefore, in this review, we have attempted to set spotlight on the most recent and landmark discoveries which have leveraged our understanding related to TRAIL-mediated signaling altogether to a new level.

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JDP2 is directly regulated by ATF4 and modulates TRAIL sensitivity by suppressing the ATF4–DR5 axis

Cited by 9 publications

References 34 publications

A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response

A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response

Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

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