Abstract:
:Aberrant glycogen synthase kinase 3beta (GSK-3beta) activity is associated with the progression of several pathological conditions such as diabetes, Alzheimer's, and cancer. GSK-3beta regulates cellular processes by directly phosphorylating metabolic enzymes and transcription factors. Here, we discovered a new target for GSK-3beta phosphorylation: the human glucocorticoid receptor (GR). Glucocorticoid signaling is essential for life and regulates diverse biological functions from cell growth to metabolism to apoptosis. Specifically, we found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta. Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB. Furthermore, GSK-3beta-mediated GR phosphorylation inhibited glucocorticoid-dependent NF-kappaB transrepression and attenuated the glucocorticoid-dependent cell death of osteoblasts. Collectively, our results describe a novel convergence point of the GSK-3beta and the GR pathways, resulting in altered hormone-regulated signaling. Our results also provide a mechanism by which GSK-3beta activity can dictate how cells will ultimately respond to glucocorticoids.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Galliher-Beckley AJ,Williams JG,Collins JB,Cidlowski JAdoi
10.1128/MCB.00808-08subject
Has Abstractpub_date
2008-12-01 00:00:00pages
7309-22issue
24eissn
0270-7306issn
1098-5549pii
MCB.00808-08journal_volume
28pub_type
杂志文章abstract::The human splicing factor 2, also called human alternative splicing factor (hASF), is the prototype of the highly conserved SR protein family involved in constitutive and regulated splicing of metazoan mRNA precursors. Here we report that the Drosophila homologue of hASF (dASF) lacks eight repeating arginine-serine di...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.4.1345-1359.2001
更新日期:2001-02-01 00:00:00
abstract::The tissue-specific expression of immunoglobulin genes can be partially explained by a requirement for activating factors found only in B lymphocytes and their derivatives. However, loss of immunoglobulin expression upon fusion of an immunoglobulin-producing myeloma cell with a T lymphoma cell (BW5147) or fibroblast (...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.5.1932
更新日期:1988-05-01 00:00:00
abstract::We have constructed a size variant of the Drosophila hsp28 gene by deleting 207 base pairs of the protein coding region, beginning 33 base pairs downstream of the ATG protein initiation codon. After transformation of Drosophila melanogaster rosy (ry506) flies with this altered gene, using the P transposable element sy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.12.2883
更新日期:1984-12-01 00:00:00
abstract::The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5725
更新日期:1993-09-01 00:00:00
abstract::The level of phosphotyrosine in vinculin was determined in chicken embryo fibroblasts transformed by various strains of avian sarcoma virus. As previously reported (Sefton et al., Cell 24:165-174, 1981), vinculin was phosphorylated at tyrosine residues in most cultures examined, but the level varied greatly and no det...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.1.263
更新日期:1985-01-01 00:00:00
abstract::Transcription of the c-rel proto-oncogene was induced transiently when resting mouse NIH 3T3 fibroblasts were stimulated with serum or phorbol-12-myristate-13-acetate. Addition of cycloheximide increased the steady-state levels of c-rel mRNA. These results indicate that c-rel is another member of the early-response ge...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.11.5239
更新日期:1989-11-01 00:00:00
abstract::Recent advancements in genetic and proteomic technologies have revealed that more of the genome encodes proteins than originally thought possible. Specifically, some putative long noncoding RNAs (lncRNAs) have been misannotated as noncoding. Numerous lncRNAs have been found to contain short open reading frames (sORFs)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.00528-19
更新日期:2020-02-27 00:00:00
abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.01454-13
更新日期:2014-04-01 00:00:00
abstract::The "pocket" proteins pRb, p107, and p130 are a family of negative growth regulators. Previous studies have demonstrated that overexpression of pRb can repress transcription by RNA polymerase (Pol) I. To assess whether pRb performs this role under physiological conditions, we have examined pre-rRNA levels in cells fro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.21.17.5806-5814.2001
更新日期:2001-09-01 00:00:00
abstract::A new retrovirus vector containing the gene for hygromycin B resistance (hyg) as a selectable marker under the control of an internal simian virus 40 promoter was constructed. It was used, together with an analogous previously described vector, DO1, which contains the gene for G418 resistance, to introduce and express...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.11.3923
更新日期:1987-11-01 00:00:00
abstract::We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00019-15
更新日期:2015-08-01 00:00:00
abstract::Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the eff...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.8.4117
更新日期:1996-08-01 00:00:00
abstract::A synthetic DNA probe designed to detect coding sequences for platelet factor 4 and connective tissue-activating peptide III (two human platelet alpha-granule proteins) was used to identify several similar sequences in total human DNA. Sequence analysis of a corresponding 3,201-base-pair EcoRI fragment isolated from a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.4.1445
更新日期:1989-04-01 00:00:00
abstract::Recombinant type 1 transforming growth factor beta (TGF-beta) was expressed to high levels in CHO cells by using dihydrofolate reductase (dhfr) gene amplification. The expression plasmid was derived from the pSV2 vectors and contained, in tandem, the simian TGF-beta and mouse dhfr cDNAs. Transcription of both cDNAs wa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.10.3418
更新日期:1987-10-01 00:00:00
abstract::By using a retrovirus-derived vector system, we generated derivatives of the human colon cancer cell line HT29 that stably overexpress a full-length cDNA encoding the beta 1 isoform of rat protein kinase C (PKC). Two of these cell lines, PKC6 and PKC7, displayed an 11- to 15-fold increase in PKC activity when compared...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.9.4650
更新日期:1990-09-01 00:00:00
abstract::The importance of c-myc as a target of the Blimp-1 repressor has been studied in BCL-1 cells, in which Blimp-1 is sufficient to trigger terminal B-cell differentiation. Our data show that Blimp-1-dependent repression of c-myc is required for BCL-1 differentiation, since constitutive expression of c-Myc blocked differe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.23.8684-8695.2000
更新日期:2000-12-01 00:00:00
abstract::Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6068
更新日期:1994-09-01 00:00:00
abstract::SCF complexes are E3 ubiquitin-protein ligases that mediate degradation of regulatory and signaling proteins and control G1/S cell cycle progression by degradation of G1 cyclins and the cyclin-dependent kinase inhibitor, Sic1. Interchangeable F-box proteins bind the core SCF components; each recruits a specific subset...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.5.1579-1588.2006
更新日期:2006-03-01 00:00:00
abstract::RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00560-08
更新日期:2008-10-01 00:00:00
abstract::Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5032-5040.2000
更新日期:2000-07-01 00:00:00
abstract::Transcriptional silencing in Saccharomyces cerevisiae occurs at specific loci and is mediated by a multiprotein complex that includes Rap1p and the Sir proteins. We studied the function of a recently identified gene, DOT4, that disrupts silencing when overexpressed. DOT4 encodes an ubiquitin processing protease (hydro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6608
更新日期:1999-10-01 00:00:00
abstract::The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis. To identify the molecular determinants that specify substrate recognition by PKR, we perf...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.4146
更新日期:1997-07-01 00:00:00
abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2661-2674.2006
更新日期:2006-04-01 00:00:00
abstract::Skp2B, an F-box protein of unknown function, is frequently overexpressed in breast cancer. In order to determine the function of Skp2B and whether it has a role in breast cancer, we performed a two-hybrid screen and established transgenic mice expressing Skp2B in the mammary glands. We found that Skp2B interacts with ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01239-07
更新日期:2007-11-01 00:00:00
abstract::The c-ABL tyrosine kinase is activated following either the loss or mutation of its Src homology domain 3 (SH3), resulting in both increased autophosphorylation and phosphorylation of cellular substrates and cellular transformation. This suggests that the SH3 domain negatively regulates c-ABL kinase activity. For seve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.12.7054
更新日期:1996-12-01 00:00:00
abstract::Throughout life, intestinal Lgr5+ stem cells give rise to proliferating transient amplifying cells in crypts, which subsequently differentiate into one of the five main cell types and migrate along the crypt-villus axis. These dynamic processes are coordinated by a relatively small number of evolutionarily conserved s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06288-11
更新日期:2012-05-01 00:00:00
abstract::The expression of the Drosophila segmentation gene fushi tarazu (ftz) is controlled at the level of transcription. The proximal enhancer, located approximately 3.4 kb upstream of the transcription start site, directs lacZ fusion gene expression in a ftz-like seven-stripe pattern in transgenic fly embryos. We have take...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5549
更新日期:1993-09-01 00:00:00
abstract::A Dictyostelium discoideum cDNA encoding an alpha-type subunit of casein kinase II was isolated, and its cDNA was used to study developmental expression of casein kinase II during the Dictyostelium life cycle. The 1.3-kb cDNA insert contained an open reading frame of 337 amino acids (M(r) 39,900). The deduced amino ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.12.5711
更新日期:1992-12-01 00:00:00
abstract::Induction of differentiation in one type of clone of mouse myeloid leukemic cells by mouse or human interleukin 6 (IL-6) and in another type of clone by mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to be associated with induction of IL-6 and GM-CSF mRNA and protein. The results indicated t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.4109
更新日期:1989-09-01 00:00:00
abstract::The micronemal protein 2 (MIC2) of Toxoplasma gondii shares sequence and structural similarities with a series of adhesive molecules of different apicomplexan parasites. These molecules accumulate, through a yet unknown mechanism, in secretory vesicles (micronemes), which together with tubular and membrane structures ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.19.7332-7341.2000
更新日期:2000-10-01 00:00:00