Amino Acid Limitation Induces Expression of CHOP, a CCAAT/Enhancer Binding Protein-related Gene, at Both Transcriptional and Post-transcriptional Levels

Bruhat, Alain; Jousse, Céline; Wang, Xiao Zhong; Ron, David; Ferrara, Marc; Fafournoux, Pierre

doi:10.1074/jbc.272.28.17588

Cited by 193 publications

(149 citation statements)

References 45 publications

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“…Leucine starvation regulates the transcription or stability of several mRNAs (Bruhat et al, 1997;Peng et al, 2002). However, cytoplasmic cyclin D1 mRNA levels were unchanged even after 4 h leucine starvation (Figure 2f), although cyclin D1 protein levels had decreased substantially (Figure 2d).…”

Section: Resultsmentioning

confidence: 98%

Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1

2007

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There is currently substantial interest in the regulation of cell function by mammalian target of rapamycin (mTOR), especially effects linked to the rapamycin-sensitive mTOR complex 1 (mTORC1). Rapamycin induces G 1 arrest and blocks proliferation of many tumor cells, suggesting that the inhibition of mTORC1 signaling may be useful in cancer therapy. In MCF7 breast adenocarcinoma cells, rapamycin decreases levels of cyclin D1, without affecting cytoplasmic levels of its mRNA. In some cell-types, rapamycin does not affect cyclin D1 levels, whereas the starvation for leucine (which impairs mTORC1 signaling more profoundly than rapamycin) does. This pattern correlates with the behavior of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, an mTORC1 target that regulates translation initiation). siRNA-mediated knockdown of 4E-BP1 abrogates the effect of rapamycin on cyclin D1 expression and increases the polysomal association of the cyclin D1 mRNA. Our data identify 4E-BP1 as a key regulator of cyclin D1 expression, indicate that this effect is not mediated through the changes in cytoplasmic levels of cyclin D1 mRNA and suggest that, in some cell types, interfering with the amino acid input to mTORC1, rather than using rapamycin, may inhibit proliferation.

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Section: Resultsmentioning

confidence: 98%

Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1

2007

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“…Beyond a simple ER-stress marker, Ddit3 encodes a ubiquitous transcription factor that is one of the most important components in the network of stress-inducible transcription. [33][34][35][36][37] In this regard, recent studies have identified DDIT3 as a direct regulator of numerous genes involved in the autophagic process. [38][39][40] Here, we show that the increase of transcripts levels of several autophagy-and lysosome-related genes in colchicinetreated fish paralleled that of Ddit3 mRNA supporting these previous studies.…”

Section: Discussionmentioning

confidence: 99%

Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay

et al. 2016

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Monitoring autophagic flux in vivo or in organs remains limited and the ideal methods relative to the techniques possible with cell culture may not exist. Recently, a few papers have demonstrated the feasibility of measuring autophagic flux in vivo by intraperitoneal (IP) injection of pharmacological agents (chloroquine, leupeptin, vinblastine, and colchicine). However, the metabolic consequences of the administration of these drugs remain largely unknown. Here, we report that 0.8 mg/kg/day IP colchicine increased LC3-II protein levels in the liver of fasted trout, supporting the usefulness of this drug for studying autophagic flux in vivo in our model organism. This effect was accompanied by a decrease of plasma glucose concentration associated with a fall in the mRNA levels of gluconeogenesis-related genes. Concurrently, triglycerides and lipid droplets content in the liver increased. In contrast, transcript levels of b-oxidation-related gene Cpt1a dropped significantly. Together, these results match with the reported role of autophagy in the regulation of glucose homeostasis and intracellular lipid stores, and highlight the importance of considering these effects when using colchicine as an in vivo "autophagometer."

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“…51,52. The 5 0 -untranslated region (5 0 UTR) of CHOP mRNA contains highly conserved uORF sequences among humans, mouse and hamster.…”

Section: Post-transcriptional Regulation Of Chopmentioning

confidence: 99%

Roles of CHOP/GADD153 in endoplasmic reticulum stress

2003

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Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system. However, when the ER function is severely impaired, the organelle elicits apoptotic signals. ER stress has been implicated in a variety of common diseases such as diabetes, ischemia and neurodegenerative disorders. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrestand DNA damage-inducible gene 153 (GADD153). Here, we summarize the current understanding of the roles of CHOP/ GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease.

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Amino Acid Limitation Induces Expression of CHOP, a CCAAT/Enhancer Binding Protein-related Gene, at Both Transcriptional and Post-transcriptional Levels

Cited by 193 publications

References 45 publications

Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1

Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1

Looking at the metabolic consequences of the colchicine-based in vivo autophagic flux assay

Roles of CHOP/GADD153 in endoplasmic reticulum stress

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