Animals use neutral lipids, particularly triacylglycerols (TAGs), to store energy. TAGs are universally organized into dynamic cytoplasmic structures called lipid droplets (LDs). In mammals TAG breakdown is catalysed by lipases, such as hormonesensitive lipase (HSL). LD membrane-resident proteins called perilipins (PLINs) regulate some of these lipases. The model organism Caenorhabditis elegans has a single known PLIN homologue and orthologues of most lipases including HSL. HOSL-1 (the HSL orthologue in C. elegans) is responsible for production of cryoprotective glycerol in cold conditions, in addition to its role in fasting-induced lipolysis. We employed this model of cold exposure to study the role of PLIN-1 in the regulation of HOSL-1. Our results suggest that both HOSL-1 and PLIN-1 are required for cold tolerance and for lipid breakdown in cold. However, the loss of PLIN-1 partially rescued the phenotype of hosl-1 null mutants exposed to cold, suggesting the presence of an alternative pathway generating glycerol via lipolysis. In early embryos, PLIN-1 knock-out results in accumulation of lipids and formation of cytoplasmic clusters of autophagic marker LGG-1, supporting the role of autophagy as an alternative lipolytic pathway in C. elegans, as is the case in mammals.

• MeSH
• autofagie MeSH
• Caenorhabditis elegans * MeSH
• lipolýza * MeSH
• membránové proteiny MeSH
• perilipin 1 MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membránové proteiny MeSH
• perilipin 1 MeSH

Transcription factors exert their regulatory potential on RNA polymerase II machinery through a multiprotein complex called Mediator complex or Mediator. The Mediator complex integrates regulatory signals from cell regulatory cascades with the regulation by transcription factors. The Mediator complex consists of 25 subunits in Saccharomyces cerevisiae and 30 or more subunits in multicellular eukaryotes. Mediator subunit 28 (MED28), along with MED30, MED23, MED25 and MED26, belong to presumably evolutionarily new subunits that seem to be absent in unicellular eukaryotes and are likely to have evolved together with multicellularity and cell differentiation. Previously, we have shown that an originally uncharacterized predicted gene, F28F8.5, is the true MED28 orthologue in Caenorhabditis elegans (mdt-28) and showed that it is involved in a spectrum of developmental processes. Here, we studied the proteomic interactome of MDT-28 edited as GFP::MDT-28 using Crispr/Cas9 technology or MDT-28::GFP expressed from extrachromosomal arrays in transgenic C. elegans exploiting the GFPTRAP system and mass spectrometry. The results show that MDT-28 associates with the Head module subunits MDT-6, MDT-8, MDT-11, MDT-17, MDT- 20, MDT-22, and MDT-30 and the Middle module subunit MDT-14. The analyses also identified additional proteins as preferential MDT-28 interactants, including chromatin-organizing proteins, structural proteins and enzymes. The results provide evidence for MDT-28 engagement in the Mediator Head module and support the possibility of physical (direct or indirect) interaction of MDT-28 with additional proteins, reflecting the transcription-regulating potential of primarily structural and enzymatic proteins at the level of the Mediator complex.

• MeSH
• alely MeSH
• Caenorhabditis elegans metabolismus   MeSH
• jaderné proteiny metabolismus   MeSH
• mediátorový komplex metabolismus   MeSH
• podjednotky proteinů metabolismus   MeSH
• proteiny Caenorhabditis elegans metabolismus   MeSH
• proteomika * MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• jaderné proteiny MeSH
• MDT-28 protein, C elegans MeSH Prohlížeč
• mediátorový komplex MeSH
• podjednotky proteinů MeSH
• proteiny Caenorhabditis elegans MeSH

ALKB-8 is a 2-oxoglutarate-dependent dioxygenase homologous to bacterial AlkB, which oxidatively demethylates DNA substrates. The mammalian AlkB family contains AlkB homologues denominated ALKBH1 to 8 and FTO. The C. elegans genome includes five AlkB-related genes, homologues of ALKBH1, 4, 6, 7, and 8, but lacks homologues of ALKBH2, 3, and 5 and FTO. ALKBH8 orthologues differ from other AlkB family members by possessing an additional methyltransferase module and an RNA binding N-terminal module. The ALKBH8 methyltransferase domain generates the wobble nucleoside 5-methoxycarbonylmethyluridine from its precursor 5-carboxymethyluridine and its (R)- and (S)-5-methoxycarbonylhydroxymethyluridine hydroxylated forms in tRNA Arg/UCG and tRNA Gly/UCC. The ALKBH8/ALKB-8 methyltransferase domain is highly similar to yeast TRM9, which selectively modulates translation of mRNAs enriched with AGA and GAA codons under both normal and stress conditions. In this report, we studied the role of alkb-8 in C. elegans. We show that downregulation of alkb-8 increases detection of lysosome-related organelles visualized by Nile red in vivo. Reversely, forced expression of alkb-8 strongly decreases the detection of this compartment. In addition, overexpression of alkb-8 applied in a pulse during the L1 larval stage increases the C. elegans lifespan.

• MeSH
• alkylační opravný homolog genetika   metabolismus   MeSH
• Caenorhabditis elegans embryologie   enzymologie   genetika   MeSH
• dioxygenasy metabolismus   MeSH
• dlouhověkost MeSH
• down regulace genetika   MeSH
• embryo nesavčí metabolismus   MeSH
• geneticky modifikovaná zvířata MeSH
• kyseliny ketoglutarové metabolismus   MeSH
• larva metabolismus   MeSH
• lyzozomy metabolismus   MeSH
• methyltransferasy metabolismus   MeSH
• operon MeSH
• promotorové oblasti (genetika) MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• RNA interference MeSH
• S-adenosylmethionin metabolismus   MeSH
• stárnutí metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ALKB-8 protein, C elegans MeSH Prohlížeč
• alkylační opravný homolog MeSH
• dioxygenasy MeSH
• kyseliny ketoglutarové MeSH
• methyltransferasy MeSH
• proteiny Caenorhabditis elegans MeSH
• S-adenosylmethionin MeSH
• zelené fluorescenční proteiny MeSH

Mediator is a multiprotein complex that connects regulation mediated by transcription factors with RNA polymerase II transcriptional machinery and integrates signals from the cell regulatory cascades with gene expression. One of the Mediator subunits, Mediator complex subunit 28 (MED28), has a dual nuclear and cytoplasmic localization and function. In the nucleus, MED28 functions as part of Mediator and in the cytoplasm, it interacts with cytoskeletal proteins and is part of the regulatory cascades including that of Grb2. MED28 thus has the potential to bring cytoplasmic regulatory interactions towards the centre of gene expression regulation. In this study, we identified MDT-28, the nematode orthologue of MED28, as a likely target of lysine acetylation using bioinformatic prediction of posttranslational modifications. Lysine acetylation was experimentally confirmed using anti-acetyl lysine antibody on immunoprecipitated GFP::MDT-28 expressed in synchronized C. elegans. Valproic acid (VPA), a known inhibitor of lysine deacetylases, enhanced the lysine acetylation of GFP::MDT-28. At the subcellular level, VPA decreased the nuclear localization of GFP::MDT-28 detected by fluorescencelifetime imaging microscopy (FLIM). This indicates that the nuclear pool of MDT-28 is regulated by a mechanism sensitive to VPA and provides an indirect support for a variable relative proportion of MED28 orthologues with other Mediator subunits.

• MeSH
• acetylace MeSH
• buněčné jádro účinky léků   metabolismus   MeSH
• Caenorhabditis elegans účinky léků   metabolismus   MeSH
• denzitometrie MeSH
• jaderné proteiny chemie   metabolismus   MeSH
• kyselina valproová farmakologie   MeSH
• larva účinky léků   MeSH
• lidé MeSH
• lysin metabolismus   MeSH
• mediátorový komplex chemie   metabolismus   MeSH
• proteiny Caenorhabditis elegans chemie   metabolismus   MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin * MeSH
• transport proteinů účinky léků   MeSH
• výpočetní biologie MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• jaderné proteiny MeSH
• kyselina valproová MeSH
• lysin MeSH
• MDT-28 protein, C elegans MeSH Prohlížeč
• mediátorový komplex MeSH
• proteiny Caenorhabditis elegans MeSH
• rekombinantní fúzní proteiny MeSH
• zelené fluorescenční proteiny MeSH

Production of thyroid hormone is precisely regulated in a negative feed-back mechanism that depends critically on thyroid hormone receptor β (TRβ). This mechanism decreases production of thyrotropin- releasing hormone (TRH) and thyrotropin (TSH) in the hypothalamus and pituitary gland in response to high levels of circulating thyroid hormones (TH). Despite the wealth of accumulated knowledge, it is still not clear how exactly this negative regulation is executed. The syndrome of resistance to thyroid hormone (RTH), in which the levels of TH are not properly sensed, represents naturally occurring situations in which molecular components of this regulation are displayed and may be uncovered. TRβ, which is central to this regulation, is in the majority of RTH cases mutated in a way that preserves some functions of the receptor. Approximately 150 different mutations in TRβ have been identified to date. Here, we hypothesized that additional pathogenic mutations in TRβ are likely to exist in human population and analysed clinical cases with suspected RTH. In keeping with our prediction, analysis of 17 patients from nine families led to identification of four presumed pathogenic mutations of TRβ, including a previously unknown mutation, T273R. This suggests that threonine 273 is likely to be critical for the normal function of TRβ, possibly due to its role in helix 12 mobility and interaction with coactivators, and thus supports the concept that TRβ-dependent trans-activating function is necessary for the inhibition of TRH and TSH expression in response to elevated levels of TH.

• MeSH
• hormon uvolňující thyreotropin metabolismus   MeSH
• hormony štítné žlázy metabolismus   MeSH
• hypothalamus metabolismus   MeSH
• lidé MeSH
• mutace MeSH
• thyreotropin metabolismus   MeSH
• tyreoidální hormony, receptory beta genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hormon uvolňující thyreotropin MeSH
• hormony štítné žlázy MeSH
• thyreotropin MeSH
• tyreoidální hormony, receptory beta MeSH

The prorenin receptor (ATP6AP2) is a multifunctional transmembrane protein; it is a constituent of proton-translocating V-ATPase, a non-proteolytic activator of renin and an adaptor in the Wnt/β-catenin pathway. Here, we studied vha-20, one of the two prorenin receptor homologues that are identified by sequence similarity in the C. elegans genome. We show that vha-20 (R03E1.2) is prominently expressed in the intestine, in the excretory cell and in amphid neurons, tissues critical for regulation of ion and water management. The expression of vha-20 in the intestine is dependent on NHR-31, a nuclear receptor related to HNF4. VHA-20 is indispensable for normal larval development, acidification of the intestine, and is required for nutrient uptake. Inhibition of vha-20 by RNAi leads to complex deterioration of water and pH gradients at the level of the whole organism including distention of pseudocoelome cavity. This suggests new roles of prorenin receptor in the regulation of body ion and water management and in acidification of intestinal lumen in nematodes.

• MeSH
• Caenorhabditis elegans fyziologie   MeSH
• homeostáza fyziologie   MeSH
• koncentrace vodíkových iontů MeSH
• larva fyziologie   MeSH
• polymerázová řetězová reakce MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• vakuolární protonové ATPasy genetika   metabolismus   MeSH
• voda metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny Caenorhabditis elegans MeSH
• vakuolární protonové ATPasy MeSH
• voda MeSH

Nuclear receptors (NRs), or nuclear hormone receptors (NHRs), are transcription factors that regulate development and metabolism of most if not all animal species. Their regulatory networks include conserved mechanisms that are shared in-between species as well as mechanisms that are restricted to certain phyla or even species. In search for conserved members of the NHR family in Schmidtea mediterranea, we identified a molecular signature of a class of NRs, NR2E1, in the S. mediterranea genome and cloned its complete cDNA coding sequence. The derived amino acid sequence shows a high degree of conservation of both DNA-binding domain and ligand- binding domain and a remarkably high homology to vertebrate NR2E1 and C. elegans NHR-67. Quantitative PCR detected approximately ten-fold higher expression of Smed-tlx-1 in the proximal part of the head compared to the tail region. The expression of Smed-tlx-1 is higher during fed state than during fasting. Smed-tlx-1 down-regulation by RNA interference affects the ability of the animals to maintain body plan and induces defects of brain, eyes and body shape during fasting and re-growing cycles. These results suggest that SMED-TLX-1 is critical for tissue and body plan maintenance in planaria.

• MeSH
• fylogeneze MeSH
• klonování DNA MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• omezení příjmu potravy fyziologie   MeSH
• orgánová specificita genetika   MeSH
• proteiny červů chemie   genetika   metabolismus   MeSH
• receptory cytoplazmatické a nukleární chemie   genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• RNA interference MeSH
• rozvržení tělního plánu * genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• stravovací zvyklosti fyziologie   MeSH
• Turbellaria embryologie   genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny červů MeSH
• receptory cytoplazmatické a nukleární MeSH

The C. elegans genome encodes an unexpectedly large number of NHRs, the majority of which are classified as supplementary nuclear receptors (supnrs) that are likely to have evolved from an ancestral protein related to vertebrate HNF-4. To understand the need for this large repertoire of potential ligand-activated transcription factors, we have begun to study an 18-member subgroup defined by DNA binding domain relatedness. Here we report on NHR-60, a supnr expressed ubiquitously throughout development with a distinct pattern of localization on the nuclear periphery. Both antibody staining and GFP reporter genes demonstrated high-level expression and accumulation of NHR-60 in seam cell nuclei that is dependent on NHR-23 activity. Interference with NHR-60 activity, by either RNAi or overexpression of a putative dominant negative isoform, results in embryonic and early larval lethality, including defects in seam cell development. This adds NHR-60 to the list of C. elegans NHRs playing important roles in development.

• MeSH
• buněčné jádro metabolismus   MeSH
• Caenorhabditis elegans embryologie   genetika   růst a vývoj   metabolismus   MeSH
• dominantní geny MeSH
• embryo nesavčí cytologie   embryologie   metabolismus   MeSH
• embryonální vývoj MeSH
• genom u helmintů genetika   MeSH
• larva metabolismus   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• proteiny Caenorhabditis elegans genetika   metabolismus   MeSH
• receptory cytoplazmatické a nukleární genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny metabolismus   MeSH
• reportérové geny MeSH
• RNA interference MeSH
• specificita protilátek MeSH
• vývojová regulace genové exprese MeSH
• zelené fluorescenční proteiny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• NHR-60 protein, C elegans MeSH Prohlížeč
• protein - isoformy MeSH
• proteiny Caenorhabditis elegans MeSH
• receptory cytoplazmatické a nukleární MeSH
• rekombinantní fúzní proteiny MeSH
• zelené fluorescenční proteiny MeSH

Valproic acid (2-propyl pentanoic acid) is a drug used for the treatment of epilepsy and bipolar disorder. Although very rare, side effects such as spina bifida and other defects of neural tube closure indicate that valproic acid interferes with developmental regulatory pathways. Recently obtained data show that valproic acid affects cell growth, differentiation, apoptosis and immunogenicity of cultured cancer cells and tumours. Focused studies uncovered the potential of valproic acid to interfere with multiple regulatory mechanisms including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS system. Valproic acid is emerging as a potential anticancer drug and may also serve as a molecular lead that can help design drugs with more specific and more potent effects on the one side and drugs with wide additive but weaker effects on the other. Valproic acid is thus a powerful molecular tool for better understanding and therapeutic targeting of pathways that regulate the behaviour of cancer cells.

• MeSH
• kyselina valproová analogy a deriváty   chemie   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádory farmakoterapie   genetika   MeSH
• protinádorové látky aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• teratogeny toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• kyselina valproová MeSH
• protinádorové látky MeSH
• teratogeny MeSH

BIR-1 and Survivin are highly conserved members of the inhibitor of apoptosis protein family that regulate cell division in nematodes and mammals and inhibit apoptosis in mammals. In the C. elegans genome, bir-1 is organized in an operon together with transcription and splicing cofactor CeSKIP (skp-1) and is highly expressed during embryogenesis as well as in non-dividing cells during larval development. Previously we have shown that BIR-1 regulates transcription and development and its loss-of-function phenotype overlaps with loss of function of CeSKIP and nuclear hormone receptor CHR3 (NHR-23). Here we searched for genes whose expression is affected by BIR-1 loss of function using whole-genome microarray experiments and identified several collagen genes as candidate targets of bir-1 inhibition in L1 larval stage. The decreased expression of selected collagen genes in bir-l-inhibited larvae was confirmed by quantitative RT-PCR. Next, we generated transgenic lines expressing bir-1 mRNA under a heat shock-regulated promoter and tested whether bir-1 overexpression has the potential to augment the expression of genes that showed decreased expression in worms treated with bir-1 RNAi. Overexpression of bir-1 resulted in a pronounced increase (2 to 5 times) of the expression of these genes. Our findings support the concept that BIR-1, a protein generally regarded as a mitotic factor, is involved in the regulation of transcription during normal development of C. elegans and has a strong ability to affect transcription of developmentally active genes if overexpressed.

• MeSH
• Caenorhabditis elegans genetika   růst a vývoj   MeSH
• genetická transkripce MeSH
• geny helmintů genetika   MeSH
• inhibitory apoptózy MeSH
• kolagen genetika   MeSH
• larva metabolismus   MeSH
• lidé MeSH
• mikročipová analýza MeSH
• nádorové proteiny metabolismus   MeSH
• proteiny asociované s mikrotubuly metabolismus   MeSH
• proteiny Caenorhabditis elegans metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• RNA interference MeSH
• sekvenční homologie * MeSH
• stanovení celkové genové exprese MeSH
• survivin MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bir-1 protein, C elegans MeSH Prohlížeč
• BIRC5 protein, human MeSH Prohlížeč
• inhibitory apoptózy MeSH
• kolagen MeSH
• nádorové proteiny MeSH
• proteiny asociované s mikrotubuly MeSH
• proteiny Caenorhabditis elegans MeSH
• survivin MeSH