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Serum regulation of Id1 expression by a BMP pathway and BMP responsive element.
Abstract Immediate early genes (IEGs) are expressed upon re-entry of quiescent cells into the cell cycle following serum stimulation. These genes are involved in growth control and differentiation and hence their expression is tightly controlled. Many IEGs are regulated through Serum Response Elements (SREs) in their promoters, which bind Serum Response Factor (SRF). However, many other IEGs do not have SREs in their promoters and their serum regulation is poorly understood. We have identified SRF-independent IEGs in SRF-depleted fibroblasts. One of these, Id1, was examined more closely. We mapped a serum responsi...
Source: Biochimica et Biophysica Acta - August 13, 2013 Category: Biochemistry Authors: Lewis TC, Prywes R Tags: Biochim Biophys Acta Source Type: research

Dehydroepiandrosterone sulfate mediates activation of transcription factors CREB and ATF-1 via a Gα11-coupled receptor in the spermatogenic cell line GC-2.
Abstract Dehydroepiandrosterone sulfate (DHEAS) is a circulating steroid produced in the adrenal cortex, brain, and gonads. Whereas a series of investigations attest to neuroprotective effects of the steroid in the brain, surprisingly little is known about the physiological effects of DHEAS on cells of the reproductive system. Here we demonstrate that DHEAS acting on the spermatogenic cell line GC-2 induces a time- and concentration-dependent phosphorylation of c-Src and Erk1/2 and activates the transcription factors ATF-1 and CREB. These actions are consistent with the non-classical signaling pathway of testoster...
Source: Biochimica et Biophysica Acta - August 26, 2013 Category: Biochemistry Authors: Shihan M, Kirch U, Scheiner-Bobis G Tags: Biochim Biophys Acta Source Type: research

TRAP assists membrane protein topogenesis at the mammalian ER membrane.
Abstract Membrane protein insertion and topogenesis generally occur at the Sec61 translocon in the endoplasmic reticulum membrane. During this process, membrane spanning segments may adopt two distinct orientations with either their N- or C-terminus translocated into the ER lumen. While different topogenic determinants in membrane proteins, such as flanking charges, polypeptide folding, and hydrophobicity, have been identified, it is not well understood how the translocon and/or associated components decode them. Here we present evidence that the translocon-associated protein (TRAP) complex is involved in membrane...
Source: Biochimica et Biophysica Acta - September 5, 2013 Category: Biochemistry Authors: Sommer N, Junne T, Spiess M, Hartmann E Tags: Biochim Biophys Acta Source Type: research

Matriptase is required for the Active Form of Hepatocyte Growth Factor Induced Met, Focal Adhesion Kinase and Protein Kinase B Activation on Neural Stem/Progenitor Cell Motility.
Abstract Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kin...
Source: Biochimica et Biophysica Acta - March 28, 2014 Category: Biochemistry Authors: Fang JD, Lee SL Tags: Biochim Biophys Acta Source Type: research

Non-classical testosterone signaling is mediated by a G-protein-coupled receptor interacting with Gnα11.
Abstract Testosterone is known to mediate its effects by two different mechanisms of action. In the so-called "classical" pathway testosterone binds to cytosolic androgen receptors (AR), which essentially function as ligand-activated transcription factors. Once activated, these receptors bind to DNA and activate the expression of target genes. In the "non-classical" pathway, the steroid hormone binds to receptors associated with the plasma membrane and induces signaling cascades mediated through activation of Erk1/2. The precise nature of the membrane-associated AR, however, remains controversial. Although some as...
Source: Biochimica et Biophysica Acta - June 1, 2014 Category: Biochemistry Authors: Shihan M, Bulldan A, Scheiner-Bobis G Tags: Biochim Biophys Acta Source Type: research

Inhibitory effects of long noncoding RNA MEG3 on hepatic stellate cells activation and liver fibrogenesis.
Abstract Long noncoding RNAs (lncRNAs) are being increasingly recognized as major players in governing fundamental biological processes through diverse mechanisms. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA correlated with several human cancers. Recently, the methylation-dependent downregulation of MEG3 has been described in liver cancers. However, its biological functional role in liver fibrosis remain unknown. In our study, MEG3 levels were remarkably decreased in CCl4-induced mouse liver fibrosis models and human fibrotic livers as demonstrated by real-time qu...
Source: Biochimica et Biophysica Acta - September 5, 2014 Category: Biochemistry Authors: He Y, Wu YT, Huang C, Meng XM, Ma TT, Wu BM, Xu FY, Zhang L, Lv XW, Li J Tags: Biochim Biophys Acta Source Type: research

CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains.
In this study we observed that USP48, a DUB of hitherto ill-defined function identified through a siRNA screen, associates with the CSN and RelA in the nucleus. We show that USP48 trims rather than completely disassembles long K48-linked free and substrate-anchored Ub-chains, a catalytic property only shared with ataxin-3 (Atx3) and otubain-1 (OTU1), and that USP48 Ub-chain-trimming activity is regulated by casein-kinase-2 (CK2)-mediated phosphorylation in response to cytokine-stimulation. Functionally, we demonstrate for the first time the CSN and USP48 to cooperatively stabilize the nuclear pool of RelA, thereby facilita...
Source: Biochimica et Biophysica Acta - December 5, 2014 Category: Biochemistry Authors: Schweitzer K, Naumann M Tags: Biochim Biophys Acta Source Type: research

Mitochondrial function contributes to oxysterols-induced osteogenic differentiation in mouse embryonic stem cells.
This study investigated the effect of an oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on osteogenic differentiation of ESCs and the alterations to mitochondrial activity during differentiation. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity, matrix mineralization, mRNA expression of osteogenic factors, runt-related transcription factor 2, osterix, and osteocalcin, and protein levels of collagen type IA (COLIA) and osteopontin (OPN). Treatment of cells with SS increased osteoinductive activity compared to the control group. Intracellular reactive oxygen ...
Source: Biochimica et Biophysica Acta - December 15, 2014 Category: Biochemistry Authors: Kwon IK, Lee SC, Hwang Y, Heo JS Tags: Biochim Biophys Acta Source Type: research

Regulation of Chondroitin-4-Sulfotransferase (CHST11) Expression by Opposing Effects of Arylsulfatase B on BMP4 and Wnt9A.
In this report, the gene regulatory mechanism by which decline in arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) reduces CHST11 (chondroitin-4-sulfotransferase; C4ST) mRNA expression in human colonic epithelial cells and in colonic epithelium of ARSB-deficient mice is presented. ARSB controls the degradation of chondroitin 4-sulfate (C4S) by removing the 4-sulfate group at the non-reducing end of the C4S chain, but has not previously been shown to affect C4S biosynthesis. The decline in CHST11 expression following ARSB reduction is attributable to effects of ARSB on bone morphogenetic protein (BMP)4, since BMP4 ...
Source: Biochimica et Biophysica Acta - December 12, 2014 Category: Biochemistry Authors: Bhattacharyya S, Feferman L, Tobacman JK Tags: Biochim Biophys Acta Source Type: research

Role of long-chain acyl-CoA synthetase 4 in formation of polyunsaturated lipid species in hepatic stellate cells.
We report that acyl CoA synthetase (ACSL) type 4, which has a preference for PUFAs, is the only upregulated ACSL family member in activated HSCs. Inhibition of the activity of ACSL4 by siRNA-mediated knockdown or addition of rosiglitazone specifically inhibited the incorporation of deuterated arachidonic acid (AA-d8) into TAG in HSCs. In agreement with this, ACSL4 was found to be partially localized around lipid droplets (LDs) in HSCs. Inhibition of ACSL4 also prevented the large increase in PUFA-TAGs in HSCs upon activation and to a lesser extent the increase of arachidonate-containing phosphatidylcholine species. Inhibit...
Source: Biochimica et Biophysica Acta - December 9, 2014 Category: Biochemistry Authors: Tuohetahuntila M, Spee B, Kruitwagen HS, Wubbolts R, Brouwers JF, van de Lest CH, Molenaar MR, Houweling M, Helms JB, Vaandrager AB Tags: Biochim Biophys Acta Source Type: research

Activation of NADPH oxidase mediates increased endoplasmic reticulum stress and left ventricular remodeling after myocardial infarction in rabbits.
In this study, we proposed to test whether activation of NADPH oxidase in the remote non-infarcted myocardium mediates ER stress and left ventricular (LV) remodeling after MI. Rabbits with MI or sham operation were randomly assigned to orally receive an NADPH oxidase inhibitor apocynin or placebo for 30days. The agents were administered beginning at 1week after surgery. MI rabbits exhibited decreases in LV fractional shortening, LV ejection fraction and the first derivative of the LV pressure rise, which were abolished by apocynin treatment. NADPH oxidase Nox2 protein and mRNA expression was increased in the remote non-inf...
Source: Biochimica et Biophysica Acta - January 20, 2015 Category: Biochemistry Authors: Li B, Tian J, Sun Y, Xu TR, Chi RF, Zhang XL, Hu XL, Zhang YA, Qin FZ, Zhang WF Tags: Biochim Biophys Acta Source Type: research

The Nav1.2 channel is regulated by GSK3.
CONCLUSION: These findings provide evidence for a new mechanism by which GSK3 modulates Nav channel function via its C-terminal tail. GENERAL SIGNIFICANCE: These findings provide fundamental knowledge in understanding signaling dysfunction common in several neuropsychiatric disorders. PMID: 25615535 [PubMed - as supplied by publisher]
Source: Biochimica et Biophysica Acta - January 20, 2015 Category: Biochemistry Authors: James TF, Nenov MN, Wildburger NC, Lichti C, Luisi J, Vergara F, Panova-Electronova NI, Nilsson CL, Rudra J, Green TA, Labate D, Laezza F Tags: Biochim Biophys Acta Source Type: research

The flavo-oxidase QSOX1 supports vascular smooth muscle cell migration and proliferation: evidence for a role in neointima growth.
Abstract Quiescin sulfhydryl oxidase 1 (QSOX1) is a flavoenzyme largely present in the extracellular milieu whose physiological functions and substrates are not known. QSOX1 has been implicated in the regulation of tumor cell survival, proliferation and migration, in addition to extracellular matrix (ECM) remodeling. However, data regarding other pathophysiological conditions are still lacking. Arterial injury by balloon catheter is an established model of post-angioplasty restenosis. This technique induces neointima formation due to migration and proliferation of vascular smooth muscle cells (VSMC), followed by E...
Source: Biochimica et Biophysica Acta - March 9, 2015 Category: Biochemistry Authors: Borges BE, Appel MH, Cofré AR, Prado ML, Steclan CA, Esnard F, Zanata SM, Laurindo FR, Nakao LS Tags: Biochim Biophys Acta Source Type: research

Protein kinase CK2 potentiates translation efficiency by phosphorylating eIF3j at Ser127.
Abstract In eukaryotic protein synthesis the translation initiation factor 3 (eIF3) is a key player in the recruitment and assembly of the translation initiation machinery. Mammalian eIF3 consists of 13 subunits, including the loosely associated eIF3j subunit that plays a stabilizing role in the eIF3 complex formation and interaction with the 40S ribosomal subunit. By means of both co-immunoprecipitation and mass spectrometry analyses we demonstrate that the protein kinase CK2 interacts with and phosphorylates eIF3j at Ser127. Inhibition of CK2 activity by CX-4945 or down-regulation of the expression of CK2 cataly...
Source: Biochimica et Biophysica Acta - April 14, 2015 Category: Biochemistry Authors: Borgo C, Franchin C, Salizzato V, Cesaro L, Arrigoni G, Matricardi L, Pinna LA, Donella-Deana A Tags: Biochim Biophys Acta Source Type: research

Insulin increases glomerular filtration barrier permeability through PKGIα-dependent mobilization of BKCa channels in cultured rat podocytes.
Abstract Podocytes are highly specialized cells that wrap around glomerular capillaries and comprise a key component of the glomerular filtration barrier. They are uniquely sensitive to insulin; like skeletal muscle and fat cells, they exhibit insulin-stimulated glucose uptake and express glucose transporters. Podocyte insulin signaling is mediated by protein kinase G type I (PKGI), and it leads to changes in glomerular permeability to albumin. Here, we investigated whether large-conductance Ca(2+)-activated K(+) channels (BKCa) were involved in insulin-mediated, PKGIα-dependent filtration barrier permeability. I...
Source: Biochimica et Biophysica Acta - May 4, 2015 Category: Biochemistry Authors: Piwkowska A, Rogacka D, Audzeyenka I, Kasztan M, Angielski S, Jankowski M Tags: Biochim Biophys Acta Source Type: research

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