Abstract:
:Nur77 (NR4A1) plays an important role in various inflammatory responses. Nur77 is rapidly degraded in cells and its protein level is critically controlled. Although few E3 ligases regulating the Nur77 protein have been defined, the deubiquitinase (DUB) responsible for Nur77 stability has not been reported to date. We identified ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1) as a DUB that stabilizes Nur77 by preventing its proteasomal degradation. We found that OTUB1 interacted with Nur77 to deubiquitinate it, thereby stabilizing Nur77 in an Asp88-dependent manner. This suggests that OTUB1 targets Nur77 for deubiquitination via a non-canonical mechanism. Functionally, OTUB1 inhibited TNFα-induced IL-6 production by promoting Nur77 protein stability. OTUB1 modulated the stability of Nur77 as a counterpart of tripartite motif 13 (Trim13). That is, OTUB1 reduced the ubiquitination and degradation of Nur77 potentiated by Trim13. In addition, this DUB also inhibited IL-6 production, which was further amplified by Trim13 in TNFα-induced responses. These findings suggest that OTUB1 is an important regulator of Nur77 stability and plays a role in controlling the inflammatory response.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Pei HZ,Huang B,Chang HW,Baek SHdoi
10.1016/j.cellsig.2019.03.018subject
Has Abstractpub_date
2019-07-01 00:00:00pages
85-95eissn
0898-6568issn
1873-3913pii
S0898-6568(19)30061-0journal_volume
59pub_type
杂志文章abstract::Long-term amino acid starvation represents a form of metabolic stress which stimulates gene expression. Here we report that depriving HeLa cells for any one of a series of amino acids activates c-Jun N-terminal kinase-1 (JNK-1). In contrast, the other mitogen-activated protein kinases (MAPKs) ERK-1 and, to a lesser ex...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00159-0
更新日期:2001-06-01 00:00:00
abstract::Vav proteins are evolutionarily conserved from nematodes to mammals and play a pivotal role in many aspects of cellular signaling, coupling cell surface receptors to various effectors functions. In mammals, there are three family members; Vav1 is specifically expressed in the hematopoietic system, whereas Vav2 and Vav...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(03)00110-4
更新日期:2004-01-01 00:00:00
abstract::Actinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis - cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulat...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109552
更新日期:2020-05-01 00:00:00
abstract::Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates a...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2014.08.019
更新日期:2014-12-01 00:00:00
abstract::Self-renewing divisions of normal and cancerous stem cells are responsible for the initiation and maintenance of normal and certain cancerous tissues, respectively. Recent findings suggest that tumor surveillance mechanisms can reduce regenerative capacity and frequency of normal stem cells, thereby contributing to ti...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2007.06.021
更新日期:2007-12-01 00:00:00
abstract::Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their h...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.03.003
更新日期:2018-07-01 00:00:00
abstract::Hepatocyte membranes from both lean and obese Zucker rats exhibited adenylate cyclase activity that could be stimulated by glucagon, forskolin, NaF and elevated concentrations of p[NH]ppG. In membranes from lean animals, functional Gi was detected by the ability of low concentrations of p[NH]ppG to inhibit forskolin-a...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90016-8
更新日期:1989-01-01 00:00:00
abstract::In this report, we examined the role of activin in the regulation of cell growth inhibition of human hepatocarcinoma cells. Using RNase protection assay for various cell cycle regulators and Western blotting experiments, we show that activin treatment of HepG2 cells leads to increased gene expression of the cyclin-dep...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2003.11.002
更新日期:2004-06-01 00:00:00
abstract::The p75 neurotrophin receptor (p75(NTR)) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To evaluate the influence of p75(NTR) in breast cancer development, we have established and characterized breast cancer cells which stably overe...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.07.014
更新日期:2010-12-01 00:00:00
abstract::The upstream stimulatory factors 1 (USF1) and 2 (USF2) are transcription factors which bind to E-box motifs of various promoters regulating a variety of different cellular processes. Only little is known about the regulation of USFs. Here, we identified protein kinase CK2 as an enzyme that phosphorylates USF1 but not ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.08.028
更新日期:2014-12-01 00:00:00
abstract::Extracellular-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) regulated by a wide range of mitogens and cellular stresses. Since its cloning in 1995, the lack of biological tools, including antibodies and specific inhibitors, have made it one of the least studied MAPK subfamilies. The di...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2005.11.003
更新日期:2006-06-01 00:00:00
abstract::In this study, we showed that nitric oxide (NO) donors induced the mesangial cell proliferation and cyclooxygenase-2 (COX-2) protein expression in murine mesangial cells. An inflammatory condition [lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)] could also induce cell proliferation and significantly enhanc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.11.015
更新日期:2005-08-01 00:00:00
abstract::The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac hypertrophy is thought to occur through its ability to inhibit the chronic GPCR signaling that promotes pathogenic growth both in vivo and in cultured cardiomyocytes. However, RGS2 is known to have additional functions beyond its activity as...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.006
更新日期:2014-06-01 00:00:00
abstract::Inflammatory stimulus during development increases the risk for adverse neurologic outcome. One possible mechanism is disrupting neuronal migration. Using lipopolysaccharide (LPS)-treatment to assess inflammatory stimulus on neuronal migration of cerebellar granule neurons, we previously found that LPS-activation incr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.10.017
更新日期:2011-02-01 00:00:00
abstract::Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in vivo. In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis. However, little is known on the expression patter...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.01.007
更新日期:2016-07-01 00:00:00
abstract::The human ether-a-go-go related gene (HERG) potassium channel has elicited intense scientific interest due to its role in cardiac repolarization and its association with arrhythmia and sudden cardiac death. Increasing evidence indicates the involvement of HERG channels in the pathophysiology of cancer. In the present ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.010
更新日期:2010-01-01 00:00:00
abstract::Endogenous reactive oxygen species (ROS) control is important for the maintenance of self-renewal of embryonic stem (ES) cells. Although miRNAs have been found to be critically involved in the regulation of the self-renewal, whether miRNAs can regulate the signaling axis to control ROS in ES cells is unclear. Here we ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.03.010
更新日期:2014-07-01 00:00:00
abstract::Small ubiquitin-like modifier (SUMO) 2 is a small protein that controls the activity and stability of other proteins by SUMOylation. In this study, T cell-specific SUMO2 overexpressing transgenic mice were generated to study the effect of SUMO2 on T lymphocytes. SUMO2 overexpression promoted differentiation of interle...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.03.001
更新日期:2015-06-01 00:00:00
abstract::The striking clinical benefit of PTH in osteoporosis began a new era of skeletal anabolic agents. Several studies have been performed, new studies are emerging out and yet controversies remain on PTH anabolic action in bone. This review focuses on the molecular aspects of PTH and PTHrP signaling in light of old player...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2009.02.012
更新日期:2009-08-01 00:00:00
abstract::We report on a novel method to monitor changes in intracellular cAMP concentration ([cAMP]i) within intact living cells using a chimeric fusion of the catalytic subunit of cAMP-dependent protein kinase to green fluorescent protein (PKAcat-GFP). In stably transfected unstimulated fibroblasts, fusion protein fluorescenc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.01.006
更新日期:2004-08-01 00:00:00
abstract::Tyrosine phosphorylation (Tyr-P) of focal adhesion kinase (FAK) regulates FAK activation. Phosphorylated FAK Tyr 397 binds Src family kinases (Src), which in turn directly phosphorylate FAK Tyr 576/577 to produce maximal FAK enzymatic activity. CB₁ cannabinoid receptors (CB₁) are abundantly expressed in the nervous sy...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.03.020
更新日期:2013-08-01 00:00:00
abstract::A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidenc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.06.015
更新日期:2018-10-01 00:00:00
abstract::Growing evidence shows that chronic inflammation drives the progression of colorectal cancer (CRC). Cyclooxygenase-2 (COX-2) is one of the most important inflammatory genes involved in solid tumor metastasis. Epidermal growth factor receptor (EGFR) also plays a key role in cancer cell development. We compared the expr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.08.017
更新日期:2012-01-01 00:00:00
abstract::Ubiquitination controls multiple cellular processes relevant to cancer pathogenesis. Using Gene Set Enrichment Analysis of an mRNA transcriptome dataset, we have identified genes encoding components of the ubiquitin system that are differentially expressed in colorectal cancers as compared to normal colonic mucosa. Am...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.08.012
更新日期:2013-01-01 00:00:00
abstract::Whole-cell currents activated by bath applications of acetylcholine (ACh) (10-30 microM) were recorded from patch-clamped myotubes of the mouse C2 cell line. Increasing concentrations of forskolin caused a dose-dependent fast decay of ACh-activated currents as compared to the long-lasting ACh-currents in control cells...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90064-h
更新日期:1990-01-01 00:00:00
abstract::Previous studies have shown that RGS4 associates with the C-termini of μ- and δ-opioid receptors in living cells and plays a key role in Gi/Go protein coupling selectivity and signalling of these receptors [12,20]. To deduce whether similar effects also occur for the κ-opioid receptor (κ-ΟR) and define the ability of ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.023
更新日期:2015-01-01 00:00:00
abstract::The adaptor protein Gab-2 coordinates the assembly of the IL-3 signalsome comprising Gab-2, Grb2, Shc, SHP-2 and PI3K. To investigate the role of the pleckstrin homology domain of Gab-2 in this process, epitope-tagged wild type Gab-2 (WTGab-2), Gab-2 lacking its PH domain (DeltaPHGab-2) and the Gab-2 PH domain alone (...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.09.002
更新日期:2006-08-01 00:00:00
abstract::Glioblastoma (GBM) is an aggressive and devastating primary brain cancer which responds very poorly to treatment. The average survival time of patients is only 14-15 months from diagnosis so there is a clear and unmet need for the development of novel targeted therapies to improve patient outcomes. The multifunctional...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2020.109638
更新日期:2020-08-01 00:00:00
abstract::When oxygen sensing cells are excited by hypoxia, background K+ currents are inhibited. TASK-1, which is commonly expressed in oxygen sensing cells and makes a background K+ current, is inactivated by hypoxia. Thus TASK-1 is a candidate molecule responsible for hypoxic excitation. However, TASK-1 per se cannot sense o...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.05.025
更新日期:2006-04-01 00:00:00
abstract::Exposure of brown fat cells to phenylephrine, an agonist of alpha-1 adrenergic receptors, activates a phospholipase A2 which releases arachidonic acid. Since receptor activation of phospholipase A2 requires calcium, experiments were undertaken to define more precisely the role played by calcium in the regulation of en...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(89)90069-7
更新日期:1989-01-01 00:00:00