High expression of the peroxisome proliferator-activated receptor α (PPARα) differentiates brown fat from white, and is related to its high capacity lipid oxidation. We analyzed effects PPARα activation on fat-specific uncoupling protein-1 (ucp-1) gene. Activators increased UCP-1 mRNA levels severalfold both in primary adipocytes vivo. Transient transfection assays indicated that (−4551)UCP1-CAT construct, containing 5′-regulatory region rat ucp-1 gene, was activated by co-transfection a...

Abstract Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, abnormal Ccnd1·Cdk4 expression promotes tumour growth metastasis. While different nuclear targets participating in tissue development have been identified, little is known about how controls adherence invasion. Here, we show that the focal adhesion component paxillin cytoplasmic substrate of Ccnd1·Cdk4. This complex phosphorylates fraction...

Kidney fibrosis is a highly deleterious process and final manifestation of chronic kidney disease. Alpha-(α)-synuclein (SNCA) an actin-binding neuronal protein with various functions within the brain; however, its role in other tissues unknown. Here, we describe expression SNCA renal epithelial cells demonstrate decrease tubules murine human fibrotic kidneys, as well downregulation proximal tubular (RPTECs) after TGF-β1 treatment. shRNA-mediated knockdown RPTECs results de novo vimentin...

β-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified β-glucan from a selected barley line and tested their effects primary dermal fibroblasts. Unexpectedly, observed that compound promoted short-transitory proliferation arrest at 24 h after its addition on medium. We determined transitory was dependent cell-cycle regulator protein Retinoblastoma. Moreover, fibroblasts increase migration capacities addition. Also, described...

// Noel P. Fusté 1,4,* , Esmeralda Castelblanco 2,5,* Isidre Felip 2,4,* Maria Santacana 2,5 Rita Fernández-Hernández 1,4 Sònia Gatius Neus Pedraza Judit Pallarés Tània Cemeli Joan Valls 3 Marc Tarres Francisco Ferrezuelo Xavier Dolcet 2,4 Matias-Guiu 2,4,5 and Eloi Garí 1 Department of Cell Cycle, Lleida, Catalonia, Spain 2 Oncological Pathology, Biostatistics Epidemiology Unit the Institut de Recerca Biomèdica Lleida (IRBLLEIDA), 4 Basic Medical Sciences at University 5 Pathology Molecular...

Uncoupling protein-3 (UCP3) gene is a member of the mitochondrial carrier superfamily preferentially expressed in skeletal muscle and up-regulated by fatty acids. Peroxisome proliferator-activated receptor (PPAR)alpha PPARdelta (also known as PPARbeta) mediate human UCP3 regulation acids through direct-repeat (DR-1) element promoter. DR-1 mutation renders promoter unresponsive to PPAR ligand vitro consistently blocks induction vivo. Although they act separate sites promoter, MyoD...

The uncoupling protein-3 (UCP-3) gene encodes for a mitochondrial protein expressed preferentially in skeletal muscle. UCP-3 mRNA is cultured muscle cells (C2C12 or L6E9) only when differentiated, at which stage highly induced by all-trans retinoic acid (RA). Here we report that human promoter activity dependent on MyoD and inducible all trans-RA. action of trans-RA increased co-transfection with RA receptor (RAR). We have characterized the response element controls induction 5' noncoding...

The transcription of the human UCP3 (uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes thyroid status also modulate expression, albeit unknown mechanisms. We created transgenic mice bearing entire investigate effect hormones on expression. Treatment with induced expression muscle. In addition, transient transfection experiments demonstrate that activate promoter when MyoD and TR (thyroid hormone...

The regulation of mRNA transport is a fundamental process for cytoplasmic sorting transcripts and spatially controlled translational derepression once properly localized. There growing evidence that translation locally modulated as result specific synaptic inputs. However, the underlying molecular mechanisms regulate this are just emerging. We show KIS, serine/threonine kinase functionally related to microtubule dynamics axon development, interacts with three proteins found in RNA granules:...

Local regulation of protein synthesis allows a neuron to rapidly alter the proteome in response synaptic signals, an essential mechanism plasticity that is altered many neurological diseases. Synthesis proteins under local control and much this occurs through structures termed RNA granules. KIS kinase associates with stathmin, modulator tubulin cytoskeleton. Furthermore, found granules stimulates translation driven by β-actin 3'UTR neurites. Here we explore physiological molecular mechanisms...

Regulation of mRNA localization is a conserved cellular process observed in many types cells and organisms. Asymmetrical distribution plays particularly important role the nervous system, where local translation localized represents key mechanism synaptic plasticity. CaMKIIα very abundant detected neurites, consistent with its crucial at glutamatergic synapses. Here, we report presence isoforms that contain intron i16 dendrites, RNA granules, synaptoneurosomes from primary neurons brain....

Abstract Glioblastoma (GBM) is a highly invasive brain neoplasia with an elevated recurrence rate after surgical resection. The cyclin D1 (Ccnd1)/Cdk4–retinoblastoma 1 (RB1) axis frequently altered in GBM, leading to overproliferation by RB1 deletion or Ccnd1‐Cdk4 overactivation. High levels of also promote GBM cell invasion mechanisms that are not so well understood. purpose this work elucidate the vivo role cytoplasmic activity dissemination GBM. We show Ccnd1 activates primary human cells...

The expression of uncoupling protein (UCP)-3 mRNA in skeletal muscle is dramatically reduced during lactation mice. reduction UCP-3 levels lowers the amount mitochondria lactation. Spontaneous or abrupt weaning reverses downregulation but not levels. In lactating and virgin mice, however, fasting increases Changes occur parallel with modifications free fatty acids, which are upregulated due to fasting. Modifications energy nutritional stress dams achieved by manipulating litter sizes do...

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of gene encoding uncoupling protein 1 (UCP1) is involved this process. Our studies show that UCP2 mRNA expression does not change breeding cycle mice. In contrast, UCP3 down-regulated lactation but it recovers after weaning, parallel with UCP1 mRNA. This leads to a decrease content BAT mitochondria lactation. Lowering energy-sparing necessities lactating dams by decreasing litter size or...

The Smc5/6 complex is a highly conserved molecular machine involved in the maintenance of genome integrity. While its functions largely depend on restraining fork remodeling activity Mph1 yeast, presence an analogous Smc5/6-FANCM regulation humans remains unknown. We generated human cell lines harboring mutations NSE1 subunit complex. Point or truncations RING domain result drastically reduced protein levels, with differential contribution two zinc-coordinating centers RING. In addition,...

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved metabolic handling fatty acids way that minimizes excessive production reactive oxygen species. Fatty are powerful regulators UCP3 gene transcription. We have found role peroxisome proliferator-activated receptor-alpha (PPARalpha) on control expression depends tissue developmental stage. In adults, mRNA unaltered from PPARalpha-null mice...

Nuclear Cyclin D1 (Ccnd1) is a main regulator of cell cycle progression and proliferation. Interestingly, Ccnd1 moves to the cytoplasm at onset differentiation in neuronal precursors. However, cytoplasmic functions targets post-mitotic neurons are unknown. Here we identify α4 subunit gamma-aminobutyric acid (GABA) type A receptors (GABAARs) as an interactor target Ccnd1-Cdk4. binds intracellular loop and, together with Cdk4, phosphorylates threonine 423 serine 431. These modifications...

Thermogenic activity in brown adipose tissue (BAT) decreases during lactation; the down-regulation of gene encoding uncoupling protein 1 (UCP1) is involved this process. Our studies show that UCP2 mRNA expression does not change breeding cycle mice. In contrast, UCP3 down-regulated lactation but it recovers after weaning, parallel with UCP1 mRNA. This leads to a decrease content BAT mitochondria lactation. Lowering energy-sparing necessities lactating dams by decreasing litter size or...

E47 is a basic helix-loop-helix transcription factor involved in neuronal differentiation and survival. We had previously shown that the protein binds to E-box sequences within promoter of TrkB gene activates its transcription. Proper expression receptor plays key role development function vertebrate nervous system, altered levels have been associated with important human diseases. Here we show interacts MLK2, mixed lineage kinase (MLK) JNK-mediated activation programmed cell death. MLK2...

Glioblastoma (GBM) is the most common tumor in central nervous system adults. This neoplasia shows a high capacity of growth and spreading to surrounding brain tissue, hindering its complete surgical resection. Therefore, finding new antitumor therapies for GBM treatment priority. We have previously described that cyclin D1-CDK4 promotes dissemination through activation small GTPases RalA RalB. In this paper, we show RalB GTPase upregulated primary cells. found downregulation Ral GTPases,...

During nervous system development, the interplay between cell cycle regulation and neurogenesis is fundamental to achieve correct timing for neuronal differentiation. However, molecular players regulating this transition are poorly understood. Among these, cell-cycle regulatory cyclins their cyclin-dependent kinases (Cdks) play a pivotal role. In present work we uncover an unknown function of cyclin D1 (Ccnd1) during cortex development which independent that relies on its cytoplasmic...

Abstract Nuclear Cyclin D1 (Ccnd1) is a main regulator of cell cycle progression and proliferation. Interestingly, Ccnd1 moves to the cytoplasm at onset differentiation in neuronal precursors. However, cytoplasmic functions targets post-mitotic neurons are unknown. Here we identify α4 subunit gamma-aminobutyric acid (GABA) type A receptors (GABA Rs) as an interactor target Ccnd1·Cdk4. binds intracellular loop and, together with Cdk4, phosphorylates threonine 423 serine 431. These...