Abstract：
:Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor family and plays key roles in glucose and lipid metabolism. Its transcriptional control of target genes is mediated by ligand-dependent recruitment of coactivators. In this study, we demonstrate that a novel transcriptional modulator of PPARγ, Flightless-I (FLII) binds directly to and suppresses the transcriptional activity of PPARγ. The LXXLL motif within the leucine-rich repeat (LRR) domain of FLII interacts directly with the DNA-binding domain of PPARγ. Interestingly, in the presence of PPARγ ligands, such as rosiglitazone and SR1664, this interaction was abolished in vitro. When FLII was overexpressed, both the transcriptional activity of PPARγ and adipogenesis were suppressed significantly, whereas specific knockdown of FLII reversed these effects. Furthermore, DNA occupancy of PPARγ on its target gene promoters was enhanced by FLII knockdown, and the interaction between PPARγ and retinoid X receptor α (RXRα) was blocked by FLII. Together, these findings strongly suggest that FLII functions in PPARγ activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPARγ/RXRα complex, and FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Choi JS,Choi SS,Kim ES,Seo YK,Seo JK,Kim EK,Suh PG,Choi JHdoi
10.1016/j.cellsig.2014.11.035subject
Has Abstractpub_date
2015-03-01 00:00:00pages
614-20issue
3eissn
0898-6568issn
1873-3913pii
S0898-6568(14)00389-1journal_volume
27pub_type
杂志文章abstract：:Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.08.005
更新日期：2014-12-01 00:00:00
abstract：:Oxidative stress is an increase in the reduction potential or a large decrease in the reducing capacity of the cellular redox couples. A particularly destructive aspect of oxidative stress is the production of reactive oxygen species (ROS), which include free radicals and peroxides. Some of the less reactive of these ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2007.04.009
更新日期：2007-09-01 00:00:00
abstract：:The effects of estrogen in breast epithelial cells are mediated primarily via estrogen receptor alpha and estrogen receptor beta (ERalpha and ERbeta). Accumulating evidence implicates a role for Ca2+ and calmodulin in breast carcinoma, as well as in the function of ERalpha. Calmodulin contributes to the regulation of ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2006.08.018
更新日期：2007-03-01 00:00:00
abstract：:The ubiquitously expressed phosphoinositide 3-kinase (PI3K) family of lipid kinases control diverse cellular functions including cell survival, proliferation, metabolism and migration. Class I PI3Ks generate two distinct 3-phosphoinositide lipid messengers, PI(3,4,5)P3 (PIP3) and PI(3,4)P2, that recruit signaling effe...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2015.05.013
更新日期：2015-09-01 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：:Metastasis is the leading cause of mortality in patients with highly invasive cancers and, as such, is a major problem for medicine. It has been increasingly recognized that cancer-related inflammation plays an important role in promoting invasion and the metastatic process in which cell motility and upregulation of p...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.03.010
更新日期：2018-07-01 00:00:00
abstract：:Modulation of immune responses is an important strategy employed by pathogens to enable their survival in host organisms. Secreted immunomodulatory molecules are key weapons in the pathogen's battle with the host immune system. In this review, we will discuss the immunomodulatory effects of the phosphorylcholine-conta...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2004.05.014
更新日期：2005-01-01 00:00:00
abstract：:Endothelial cell apoptosis induced by hypoxia is implicated in the pathogenesis of vascular diseases. However, the underlying mechanism is not clearly elucidated. In this study, we found that hypoxia increased Mxi1-0 expression, and the Mxi1-0 siRNA could inhibit caspase-8 activation and apoptosis in HUVECs induced by...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.08.009
更新日期：2018-11-01 00:00:00
abstract：:To understand how a signaling molecule's activities are regulated, we need insight into the processes controlling the dynamic balance between its synthesis and degradation. For the Ins(1,3,4,5,6)P5 signal, this information is woefully inadequate. For example, the only known cytosolic enzyme with the capacity to degrad...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.05.017
更新日期：2006-04-01 00:00:00
abstract：:Bone Morphogenetic Proteins (BMPs) are potent growth factors belonging to the Transforming Growth Factor Beta superfamily. To date over 20 members have been identified in humans with varying functions during processes such as embryogenesis, skeletal formation, hematopoiesis and neurogenesis. Though their functions hav...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2010.10.003
更新日期：2011-04-01 00:00:00
abstract：:Extracellular adenine dinucleotides are modulators of blood vessel tone. We have previously demonstrated that Ap(2)A and Ap(4)A induce the synthesis of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) while Ap(3)A and Ap(5)A do not [FEBS Lett. 427 (1998) 320; Arch. Biochem. Biophys. 364 (1999) 280.]. In t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(00)00147-9
更新日期：2001-02-01 00:00:00
abstract：:The human NPY Y(1) receptor undergoes fast agonist-induced internalization via clathrin-coated pits then recycles back to the cell membrane. In an attempt to identify the molecular determinants involved in this process, we studied several C-terminal truncation mutants tagged with EFGP. In the absence of agonist, Y(1) ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.09.007
更新日期：2011-01-01 00:00:00
abstract：:Caveolin-1 (Cav-1) is a major structural protein of caveolae and plays an important role as a negative regulator of various signaling pathways such as the transforming growth factor-beta (TGF-beta)/smad pathway. In this study, we investigated the role of cav-1 on basal and TGF-beta1-induced expression of type I procol...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.02.020
更新日期：2008-07-01 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：:MAP Kinase Phosphatase-2 (MKP-2) is a dual specific nuclear phosphatase which is selective for both ERK and JNK, MAP kinases implicated in the regulation of apoptosis in response to genotoxic stress. Here we report the conditional expression of MKP-2 in human embryonic kidney cells 293. We demonstrate that Flag-WT-MKP...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.01.003
更新日期：2005-10-01 00:00:00
abstract：:The interferon regulated transcription factor IRF-1 is a tumour suppressor protein that is activated in response to viral infection and cell signalling activated by double stranded DNA lesions. IRF-1 has a short half-life (t(0.5) 20-40 min) allowing rapid changes in steady state levels by modulating its rate of degrad...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.05.004
更新日期：2009-10-01 00:00:00
abstract：:Nitric oxide (NO) is known to regulate redox-sensitive signalling pathways in physiology and pathophysiology. Depending on its concentration, the NO-releasing compound S-nitrosoglutathione (GSNO) causes negative and positive regulation of thymocyte apoptosis. At levels below 0.6 mM, GSNO produces deoxyribonucleic acid...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(95)02051-9
更新日期：1996-03-01 00:00:00
abstract：:Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults with median survival time of 14.6 months. A small fraction of cancer stem cells (CSC) initiate and maintain tumors thus driving glioma tumorigenesis and being responsible for resistance to classical chemo- and radio-therapies...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.08.020
更新日期：2014-12-01 00:00:00
abstract：:Arap3 is a phosphoinositide (PI) 3 kinase effector that serves as a GTPase activating protein (GAP) for both Arf and Rho G-proteins. The protein has multiple pleckstrin homology (PH) domains that bind preferentially phosphatidyl-inositol-3,4,5-trisphosphate (PI(3,4,5,)P3) to induce translocation of Arap3 to the plasma...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2006.12.015
更新日期：2007-06-01 00:00:00
abstract：:The molecular mechanisms that underlie non-genomic induction of the 25-hydroxyvitamin D3 24-hydroxylase (CYP24) gene promoter by the steroid hormone, 1,25-Dihydroxyvitamin D3 (1,25D), are poorly understood. Although we have previously identified a functional inverted GC-box in the early promoter at -113/-105 bp, it is...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.11.009
更新日期：2010-03-01 00:00:00
abstract：:Ras proteins function as molecular switches that are activated in response to signalling pathways initiated by various extracellular stimuli and subsequently bind to numerous effector proteins leading to the activation of several signalling cascades within the cell. Ras and Ras-related proteins belong to a large super...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2010.05.010
更新日期：2010-12-01 00:00:00
abstract：:Inositol 1,4,5-trisphosphate 5-phosphatase catalyses the dephosphorylation of the phosphate in the 5-position from inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. One particulate and two soluble enzymes were previously described in bovine brain. In this study, we have obtained a precipitating anti...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(90)90082-l
更新日期：1990-01-01 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：:SIRT1 is a highly conserved type III acetyltransferase gene located on chromosome 10 in mammals that belong to the Sirtuins family. In order to explore the effects of the SIRT1 gene in the ATDC5 cell line, an RNAi SIRT1 target sequence was designed and synthesized, aimed to knockdown the expression of SIRT1 in ATDC5 b...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.09.016
更新日期：2019-01-01 00:00:00
abstract：:GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine producti...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.01.012
更新日期：2015-04-01 00:00:00
abstract：:CyrA is a novel cysteine-rich protein with four EGFL repeats that was isolated using the calmodulin (CaM) binding overlay technique (CaMBOT), suggesting it is a CaM-binding protein (CaMBP). The full-length 63kDa cyrA is cleaved into two major C-terminal fragments, cyrA-C45 and cyrA-C40. A putative CaM-binding domain w...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.03.008
更新日期：2011-07-01 00:00:00
abstract：:Through diametric actions, the transforming growth factor beta (TGFbeta) and Angiotensin II (AngII) play important roles in regulating various biological responses such as cell proliferation and migration. Signaling initiated by TGFbeta and AngII occurs through two structurally and functionally distinct receptor super...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.01.037
更新日期：2009-06-01 00:00:00
abstract：:Neutrophils are key effector cells of the innate immune system, serving as a first line of defense in the response to injury and playing essential roles in the wound healing process. Following myocardial infarction (MI), neutrophils infiltrate into the infarct region to propagate inflammation and begin the initial pha...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109816
更新日期：2021-01-01 00:00:00
abstract：:Strategies which can be used to elucidate the nature of a GTP-binding regulatory protein (G-protein) involved in an intracellular pathway of interest in the complex environment of the cell are described and evaluated. A desirable strategy is considered to be one in which the first stage indicates a requirement for one...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(96)00131-3
更新日期：1997-05-01 00:00:00
abstract：:In cartilage, chondrocytes are responsible for the biogenesis and maintenance of the extracellular matrix (ECM) composed of proteins, glycoproteins and proteoglycans. Various cellular stresses, such as hypoxia, nutrient deprivation, oxidative stress or the accumulation of advanced glycation end products (AGEs) during ...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109880
更新日期：2021-02-01 00:00:00
