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Transcription Factor CHOP

About: Transcription Factor CHOP is a research topic. Over the lifetime, 443 publications have been published within this topic receiving 46408 citations.


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18 Mar 2016
TL;DR: In this paper, the authors used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the UORF on CHOP expression during stress.
Abstract: Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5′-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP target genes, culminating in increased cell death in response to stress.

37 citations

Journal ArticleDOI
TL;DR: This study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to Niclosamide, and indicates that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in H CC cells.
Abstract: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It’s suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.

36 citations

Journal ArticleDOI
TL;DR: The combined effect of vorinostat, which has a potent inhibitory effect for HDAC6, with CAM and BZ in breast cancer cell lines, and expression levels of ER-stress-related genes were maximally induced by the simultaneous combination of three reagents suggest that simultaneous targeting of intracellular proteolytic pathways andHDAC6 enhances ER- stress-mediated apoptosis in breast cancers.

36 citations

Journal ArticleDOI
TL;DR: Overall, the data suggest that CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo, thus implicating CHOP in sunburn cell (SBC) formation.

36 citations

Journal ArticleDOI
TL;DR: It is demonstrated that in human myxoid liposarcoma cells, wild‐type TLS binds to RNA polymerase II (Pol II) via its N‐terminal domain and to the transcription and translation factor Y‐box binding protein‐1 (YB‐1) through its C‐terminals, suggesting that aberrant RNA splicing may be a common feature of human sarcomas.

35 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20213
20203
20193
201811
201719
201648