ArticleThe Journal of biological chemistry2008
Differential control of the CCAAT/enhancer-binding protein beta (C/EBPbeta) products liver-enriched transcriptional activating protein (LAP) and liver-enriched transcriptional inhibitory protein (LIP) and the regulation of gene expression during the response to endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- C/EBPβ as a master regulator of inflammasome signaling in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2025Pooled it
- GermlineeLife · 2024Article
- GermlinebioRxiv : the preprint server for biology · 2024Article
- Role of lncRNA LIPE-AS1 in adipogenesis.Adipocyte · 2022Article
- Metformin inhibits human non-small cell lung cancer by regulating AMPK-CEBPB-PDL1 signaling pathway.Cancer immunology, immunotherapy : CII · 2022Article
- Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress.Molecular cell · 2021Article
- C/EBPβ isoforms sequentially regulate regenerating mouse hematopoietic stem/progenitor cells.Blood advances · 2020Article
- Roles of the Translation Initiation Factor eIF2α Phosphorylation in Cell Structure and Function.Cell structure and function · 2020Article
- Article
- TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis.The Journal of experimental medicine · 2020Article
- Combined Irradiation by Gamma Rays and Carbon Nuclei Increases the C/EBP-β LIP Isoform Content in the Pituitary Gland of Rats.Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections · 2019Article
- Transforming growth factor β (TGFβ) cross-talk with the unfolded protein response is critical for hepatic stellate cell activation.The Journal of biological chemistry · 2019Article
- Liver function and dysfunction - a unique window into the physiological reach of ER stress and the unfolded protein response.The FEBS journal · 2019Review
- C/EBPβ Deletion Promotes Expansion of Poorly Functional Intestinal Regulatory T Cells.Journal of Crohn's & colitis · 2018Article
- Erythropoietin-producing hepatocellular A7 triggering ovulation indicates a potential beneficial role for polycystic ovary syndrome.EBioMedicine · 2018Article
- Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer.Cell metabolism · 2018Article
- The C/EBPβ LIP isoform rescues loss of C/EBPβ function in the mouse.Scientific reports · 2018Article
- EGFR and C/EBP-β oncogenic signaling is bidirectional in human glioma and varies with the C/EBP-β isoform.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.Molecular and cellular biology · 2015Article
- cEBP Homologous Protein Expression in Macrophages Regulates the Magnitude and Duration of IL-6 Expression and Dextran Sodium Sulfate Colitis.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a stress response program that protects cells early in the response and can lead to apoptosis during prolonged stress. The basic leucine zipper transcription factor, CCAAT/enhancer-binding protein beta (C/EBPbeta), is one of the genes with increased expression during ER stress. Translation of the C/EBPbeta mRNA from different initiation codons leads to the synthesis of two transcriptional activators (LAP-1 and -2) and a transcriptional repressor (LIP). The LIP/LAP ratio is a critical factor in C/EBPbeta-mediated gene transcription. It is shown here that the LIP/LAP ratio decreased by 5-fold during the early phase of ER stress and increased by 20-fold during the late phase, mostly because of changes in LIP levels. The early decrease in LIP required degradation via the proteasome pathway and phosphorylation of the translation initiation factor, eIF2alpha. The increased LIP levels during the late phase were due to increased synthesis and increased stability of the protein. It is proposed that regulation of synthesis and degradation rates during ER stress controls the LIP/LAP ratio. The importance of C/EBPbeta in the ER-stress response program was demonstrated using C/EBPbeta-deficient mouse embryonic fibroblasts. It is shown that C/EBPbeta attenuates expression of pro-survival ATF4 target genes in late ER stress and enhances expression of cell death-associated genes downstream of CHOP. The inhibitory effect of LIP on ATF4-induced transcription was demonstrated for the cat-1 amino acid transporter gene. We conclude that regulation of LIP/LAP ratios during ER stress is a novel mechanism for modulating the cellular stress response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.