β-Galactosidase from Bacillus circulans ATCC 31382 (BgaD) is a biotechnologically important enzyme for the synthesis of β-galactooligosaccharides (GOS). Among its four isoforms, isoform A (BgaD-A) has distinct synthetic properties. Here, we present cryoelectron microscopy (cryo-EM) structures of BgaD-A and compare them with the known X-ray crystal structure of isoform D (BgaD-D), revealing substantial structural divergences between the two isoforms. In contrast to BgaD-D, BgaD-A features a flexible Big-4 domain and another enigmatic domain. The newly identified flexible region in BgaD-A is termed as "barrier domain 8," and serves as a barricade, obstructing the access of longer oligosaccharide substrates into the active site of BgaD-A. The transgalactosylation reactions catalyzed by both isoforms revealed that BgaD-A has a higher selectivity than BgaD-D in the earlier stages of the reaction and is prevailingly directed to shorter galactooligosaccharides. This study improves our understanding of the structural determinants governing β-galactosidase catalysis, with implications for tailored GOS production.

• Klíčová slova
• cryo-EM, crystal structure, galactooligosaccharide, galactosidase, structural flexibility, substrate specificity, transgalactosylation,
• MeSH
• Bacillus * enzymologie   MeSH
• bakteriální proteiny chemie   metabolismus   MeSH
• beta-galaktosidasa * chemie   metabolismus   genetika   MeSH
• elektronová kryomikroskopie * MeSH
• izoenzymy chemie   metabolismus   MeSH
• katalytická doména * MeSH
• krystalografie rentgenová MeSH
• molekulární modely * MeSH
• oligosacharidy metabolismus   chemie   MeSH
• protein - isoformy chemie   metabolismus   MeSH
• substrátová specifita MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální proteiny MeSH
• beta-galaktosidasa * MeSH
• izoenzymy MeSH
• oligosacharidy MeSH
• protein - isoformy MeSH

Maintenance of Na+ and K+ gradients across the cell plasma membrane is an essential process for mammalian cell survival. An enzyme responsible for this process, sodium-potassium ATPase (NKA), has been currently extensively studied as a potential anticancer target, especially in lung cancer and glioblastoma. To date, many NKA inhibitors, mainly of natural origin from the family of cardiac steroids (CSs), have been reported and extensively studied. Interestingly, upon CS binding to NKA at nontoxic doses, the role of NKA as a receptor is activated and intracellular signaling is triggered, upon which cancer cell death occurs, which lies in the expression of different NKA isoforms than in healthy cells. Two major CSs, digoxin and digitoxin, originally used for the treatment of cardiac arrhythmias, are also being tested for another indication-cancer. Such drug repositioning has a big advantage in smoother approval processes. Besides this, novel CS derivatives with improved performance are being developed and evaluated in combination therapy. This article deals with the NKA structure, mechanism of action, activity modulation, and its most important inhibitors, some of which could serve not only as a powerful tool to combat cancer, but also help to decipher the so-far poorly understood NKA regulation.

• Klíčová slova
• Na+/K+-ATPase activity modulation, anticancer activity, cardiac glycosides, combination therapy, digitoxigenin, digitoxin, digoxin, natural compounds, ouabain, sodium-potassium pump inhibitors,
• MeSH
• antitumorózní látky chemie   terapeutické užití   MeSH
• digitoxin chemie   terapeutické užití   MeSH
• digoxin chemie   terapeutické užití   MeSH
• glioblastom farmakoterapie   enzymologie   patologie   MeSH
• inhibitory enzymů chemie   terapeutické užití   MeSH
• izoenzymy antagonisté a inhibitory   chemie   metabolismus   MeSH
• klinické zkoušky jako téma MeSH
• konformace proteinů MeSH
• lidé MeSH
• molekulární modely MeSH
• nádory mozku farmakoterapie   enzymologie   patologie   MeSH
• nádory plic farmakoterapie   enzymologie   patologie   MeSH
• ouabain chemie   terapeutické užití   MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• sodíko-draslíková ATPasa antagonisté a inhibitory   chemie   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH
• digitoxin MeSH
• digoxin MeSH
• inhibitory enzymů MeSH
• izoenzymy MeSH
• ouabain MeSH
• sodíko-draslíková ATPasa MeSH

Tuberculosis (TB) remains one of the major health concerns worldwide. Mycobacterium tuberculosis (Mtb), the causative agent of TB, can flexibly change its metabolic processes during different life stages. Regulation of key metabolic enzyme activities by intracellular conditions, allosteric inhibition or feedback control can effectively contribute to Mtb survival under different conditions. Phosphofructokinase (Pfk) is one of the key enzymes regulating glycolysis. Mtb encodes two Pfk isoenzymes, Pfk A/Rv3010c and Pfk B/Rv2029c, which are differently expressed upon transition to the hypoxia-induced non-replicating state of the bacteria. While pfkB gene and protein expression are upregulated under hypoxic conditions, Pfk A levels decrease. Here, we present biochemical characterization of both Pfk isoenzymes, revealing that Pfk A and Pfk B display different kinetic properties. Although the glycolytic activity of Pfk A is higher than that of Pfk B, it is markedly inhibited by an excess of both substrates (fructose-6-phosphate and ATP), reaction products (fructose-1,6-bisphosphate and ADP) and common metabolic allosteric regulators. In contrast, synthesis of fructose-1,6-bisphosphatase catalyzed by Pfk B is not regulated by higher levels of substrates, and metabolites. Importantly, we found that only Pfk B can catalyze the reverse gluconeogenic reaction. Pfk B thus can support glycolysis under conditions inhibiting Pfk A function.

• Klíčová slova
• Mycobacterium tuberculosis, allosteric regulation, enzyme kinetics, glycolysis, phosphofructokinase A and B,
• MeSH
• adenosindifosfát metabolismus   farmakologie   MeSH
• adenosintrifosfát metabolismus   farmakologie   MeSH
• alosterická regulace MeSH
• bakteriální proteiny antagonisté a inhibitory   metabolismus   MeSH
• enzymová indukce MeSH
• fosfofruktokinasy antagonisté a inhibitory   metabolismus   MeSH
• fruktosadifosfáty biosyntéza   farmakologie   MeSH
• fruktosafosfáty metabolismus   farmakologie   MeSH
• glukoneogeneze MeSH
• glykolýza MeSH
• hexosafosfáty metabolismus   MeSH
• izoenzymy antagonisté a inhibitory   metabolismus   MeSH
• katalýza MeSH
• kinetika MeSH
• kyslík farmakologie   MeSH
• L-laktátdehydrogenasa metabolismus   MeSH
• Mycobacterium tuberculosis účinky léků   enzymologie   MeSH
• pyruvátkinasa metabolismus   MeSH
• rekombinantní proteiny metabolismus   MeSH
• substrátová specifita MeSH
• zpětná vazba fyziologická MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• adenosindifosfát MeSH
• adenosintrifosfát MeSH
• bakteriální proteiny MeSH
• fosfofruktokinasy MeSH
• fructose-1,6-diphosphate MeSH Prohlížeč
• fructose-6-phosphate MeSH Prohlížeč
• fruktosadifosfáty MeSH
• fruktosafosfáty MeSH
• hexosafosfáty MeSH
• izoenzymy MeSH
• kyslík MeSH
• L-laktátdehydrogenasa MeSH
• phosphofructokinase A protein, Mycobacterium tuberculosis MeSH Prohlížeč
• pyruvátkinasa MeSH
• rekombinantní proteiny MeSH
• tagatose 6-phosphate MeSH Prohlížeč

Acetylcholine (ACh)-mediated vagal transmission as well as nonneuronal ACh release are considered cardioprotective in pathological situations with increased sympathetic drive such as ischemia-reperfusion and cardiac remodeling. ACh action is terminated by hydrolysis by the cholinesterases (ChEs), acetylcholinesterase, and butyrylcholinesterase. Both ChEs exist in multiple molecular variants either soluble or anchored by specific anchoring proteins like collagen Q (ColQ) anchoring protein and proline-rich membrane anchoring protein (PRiMA). Here we assessed the expression of specific ChE molecular forms in different heart compartments using RT-qPCR. We show that both ChEs are expressed in all heart compartments but display different expression patterns. The acetylcholinesterase-T variant together with PRiMA and ColQ is predominantly expressed in rat atria. Butylcholinesterase is found in all heart compartments and is accompanied by both PRiMA and ColQ anchors. Its expression in the ventricular system suggests involvement in the nonneuronal cholinergic system. Additionally, two PRiMA variants are detected throughout the rat heart.

• Klíčová slova
• acetylcholine, acetylcholinesterase, acétylcholine, acétylcholinestérase, butyrylcholinesterase, butyrylcholinestérase, collagen Q anchoring protein, proline-rich membrane anchoring protein, « collagen Q anchoring protein », « proline-rich membrane anchoring protein »,
• MeSH
• acetylcholin metabolismus   MeSH
• acetylcholinesterasa analýza   metabolismus   MeSH
• butyrylcholinesterasa analýza   metabolismus   MeSH
• GPI-vázané proteiny analýza   metabolismus   MeSH
• izoenzymy analýza   metabolismus   MeSH
• kolagen analýza   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• membránové proteiny analýza   metabolismus   MeSH
• myokard enzymologie   MeSH
• potkani Wistar MeSH
• proteiny nervové tkáně analýza   metabolismus   MeSH
• stanovení celkové genové exprese MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholin MeSH
• acetylcholinesterasa MeSH
• Ache protein, rat MeSH Prohlížeč
• butyrylcholinesterasa MeSH
• ColQ protein, rat MeSH Prohlížeč
• GPI-vázané proteiny MeSH
• izoenzymy MeSH
• kolagen MeSH
• membránové proteiny MeSH
• PRiMA1 protein, rat MeSH Prohlížeč
• proteiny nervové tkáně MeSH

Trypanosoma brucei is an important human pathogen. In this study, we have focused on the characterization of FtsH protease, ATP-dependent membrane-bound mitochondrial enzyme important for regulation of protein abundance. We have determined localization and orientation of all six putative T.brucei FtsH homologs in the inner mitochondrial membrane by in silico analyses, by immunofluorescence, and with protease assay. The evolutionary origin of these homologs has been tested by comparative phylogenetic analysis. Surprisingly, some kinetoplastid FtsH proteins display inverted orientation in the mitochondrial membrane compared to related proteins of other examined eukaryotes. Moreover, our data strongly suggest that during evolution the orientation of FtsH protease in T. brucei varied due to both loss and acquisition of the transmembrane domain.

• Klíčová slova
• AAA protease, Evolution, FtsH, Mitochondrion, Phylogeny, Trypanosoma,
• MeSH
• Arabidopsis klasifikace   enzymologie   genetika   MeSH
• Euglena gracilis klasifikace   enzymologie   genetika   MeSH
• Euglena longa klasifikace   enzymologie   genetika   MeSH
• exprese genu MeSH
• fylogeneze MeSH
• izoenzymy chemie   genetika   metabolismus   MeSH
• konzervovaná sekvence MeSH
• Leishmania major klasifikace   enzymologie   genetika   MeSH
• lidé MeSH
• mitochondriální membrány chemie   enzymologie   MeSH
• mitochondriální proteiny chemie   genetika   metabolismus   MeSH
• mitochondrie enzymologie   genetika   MeSH
• molekulární evoluce * MeSH
• myši MeSH
• proteasy chemie   genetika   metabolismus   MeSH
• proteinové domény MeSH
• protozoální proteiny chemie   genetika   metabolismus   MeSH
• Saccharomyces cerevisiae klasifikace   enzymologie   genetika   MeSH
• Trypanosoma brucei brucei klasifikace   enzymologie   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• izoenzymy MeSH
• mitochondriální proteiny MeSH
• proteasy MeSH
• protozoální proteiny MeSH

Schistosomula (the post-infective stages) of the neurotropic schistosome Trichobilharzia regenti possess multiple isoforms of cathepsin B1 peptidase (TrCB1.1-TrCB1.6) with involvement in nutrient digestion. The comparison of substrate preferences of TrCB1.1 and TrCB1.4 showed that TrCB1.4 had a very narrow substrate specificity and after processing it was less effective toward protein substrates when compared to TrCB1.1. Self-processing of both isoforms could be facilitated by sulfated polysaccharides due to a specific binding motif in the pro-sequence. Trans-activation by heterologous enzymes was also successfully employed. Expression profiling revealed a high level of transcription of genes encoding the enzymatically inactive paralogs TrCB1.5 and TrCB1.6. The transcription level of TrCB1.6 was comparable with that of TrCB1.1 and TrCB1.2, the most abundant active isoforms. Recombinant TrCB1.6wt, a wild type paralog with a Cys29-to-Gly substitution in the active site that renders the enzyme inactive, was processed by the active TrCB1 forms and by an asparaginyl endopeptidase. Although TrCB1.6wt lacked hydrolytic activity, endopeptidase, but not dipeptidase, activity could be restored by mutating Gly29 to Cys29. The lack of exopeptidase activity may be due to other mutations, such as His110-to-Asn in the occluding loop and Asp224-to-Gly in the main body of the mature TrCB1.6, which do not occur in the active isoforms TrCB1.1 and TrCB1.4 with exopeptidase activity. The catalytically active enzymes and the inactive TrCB1.6 paralog formed complexes with chicken cystatin, thus supporting experimentally the hypothesis that inactive paralogs could potentially regulate the activity of the active forms or protect them from being inhibited by host inhibitors. The effect on cell viability and nitric oxide production by selected immune cells observed for TrCB1.1 was not confirmed for TrCB1.6. We show here that the active isoforms of TrCB1 have different affinities for peptide substrates thereby facilitating diversity in protein-derived nutrition for the parasite. The inactive paralogs are unexpectedly highly expressed and one of them retains the ability to bind cystatins, likely due to specific mutations in the occluding loop and the enzyme body. This suggests a role in sequestration of inhibitors and protection of active cysteine peptidases.

• Klíčová slova
• cathepsin B, cystatin, helminth, occluding loop, peptidase, processing, schistosome, substrate specificity,
• MeSH
• astrocyty metabolismus   MeSH
• cystatiny metabolismus   MeSH
• hydrolýza MeSH
• izoenzymy metabolismus   MeSH
• kathepsin B chemie   genetika   metabolismus   MeSH
• makrofágy metabolismus   MeSH
• myši MeSH
• oxid dusnatý metabolismus   MeSH
• prekurzory enzymů metabolismus   MeSH
• proteolýza MeSH
• RAW 264.7 buňky MeSH
• rekombinantní proteiny metabolismus   MeSH
• Schistosomatidae enzymologie   patogenita   MeSH
• substituce aminokyselin MeSH
• substrátová specifita MeSH
• vazba proteinů MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cystatin, egg-white MeSH Prohlížeč
• cystatiny MeSH
• izoenzymy MeSH
• kathepsin B MeSH
• oxid dusnatý MeSH
• prekurzory enzymů MeSH
• rekombinantní proteiny MeSH

This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the mechanism underlying the antitubercular effect of fucoxanthin. The obtained results showed that fucoxanthin showed a clear bacteriostatic action against the all Mtb strains tested, with minimum inhibitory concentrations (MIC) ranging from 2.8 to 4.1 µM, along with a good degree of selectivity index (ranging from 6.1 to 8.9) based on cellular toxicity evaluation compared with standard drug isoniazid (INH). The potent inhibitory actions of fucoxanthin and standard uridine-5'-diphosphate against UGM were recorded to be 98.2% and 99.2%, respectively. TBNAT was potently inactivated by fucoxanthin (half maximal inhibitory concentration (IC50) = 4.8 µM; 99.1% inhibition) as compared to INH (IC50 = 5.9 µM; 97.4% inhibition). Further, molecular docking approaches were achieved to endorse and rationalize the biological findings along with envisaging structure-activity relationships. Since the clinical evidence of the last decade has confirmed the correlation between bacterial infections and autoimmune diseases, in this study we have discussed the linkage between infection with Mtb and autoimmune diseases based on previous clinical observations and animal studies. In conclusion, we propose that fucoxanthin could demonstrate great therapeutic value for the treatment of tuberculosis by acting on multiple targets through a bacteriostatic effect as well as by inhibiting UGM and TBNAT. Such outcomes may lead to avoiding or decreasing the susceptibility to autoimmune diseases associated with Mtb infection in a genetically susceptible host.

• Klíčová slova
• Mycobacterium tuberculosis, UDP-galactopyranose mutase, arylamine-N-acetyltransferase, autoimmunity, fucoxanthin, marine carotenoid, pathogenesis,
• MeSH
• antituberkulotika farmakologie   MeSH
• arylamin-N-acetyltransferasa metabolismus   MeSH
• autoimunitní nemoci farmakoterapie   MeSH
• buněčná stěna účinky léků   enzymologie   MeSH
• buněčné linie MeSH
• intramolekulární transferasy metabolismus   MeSH
• izoenzymy metabolismus   MeSH
• karotenoidy farmakologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti metody   MeSH
• Mycobacterium tuberculosis účinky léků   enzymologie   MeSH
• simulace molekulového dockingu metody   MeSH
• tuberkulóza farmakoterapie   MeSH
• xanthofyly farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antituberkulotika MeSH
• arylamin-N-acetyltransferasa MeSH
• fucoxanthin MeSH Prohlížeč
• intramolekulární transferasy MeSH
• izoenzymy MeSH
• karotenoidy MeSH
• N-acetyltransferase 1 MeSH Prohlížeč
• UDP-galactopyranose mutase MeSH Prohlížeč
• xanthofyly MeSH

Ribociclib is a novel cyclin-dependent kinase (CDK) 4 and 6 selective inhibitor that recently gained breakthrough therapy status and global approval for advanced breast cancer treatment. ATP-binding cassette (ABC) transporters may become a site of severe drug interactions and a mechanism of multidrug resistance (MDR) development. With respect to rapid progress of ribociclib in the clinical field, we aimed to identify its interactions with ABC transporters and cytochrome P450 (CYP) isoenzymes and evaluate its potential to overcome transporter-mediated MDR using established in vitro methods. Our data showed accelerated ABCB1 inhibitor LY335979-sensitive, basolateral-to-apical transport of ribociclib across MDCKII-ABCB1 cell monolayers, which identified ribociclib as an ABCB1 substrate. The antiproliferative studies supported this finding by demonstrating significantly higher EC50 value in ABCB1-, but not ABCG2- or ABCC1-expressing MDCKII cells, than in the parent MDCKII cell line. Furthermore, we observed significant inhibitory effects of ribociclib on ABCB1 and ABCG2 transporters and CYP1A2, CYP3A4, CYP3A5, and CYP2C9 isoform activity in human CYP-expressing insect microsomes. The ribociclib-induced ABCB1 and ABCG2 inhibition further reversed daunorubicin and mitoxantrone resistance in MDCKII and human MCF-7 breast carcinoma cell lines, indicating a synergistic antiproliferative effect, without affecting ABCB1 or ABCG2 expression. In summary, our data indicate that ABCB1 affects ribociclib transport across the membranes and the high potential of ribociclib for drug-drug interactions (DDIs) through ABCB1 and ABCG2 transporters and CYP isoforms. Moreover, we demonstrate the beneficial MDR-reversing potential of ribociclib, which could be further exploited in novel anticancer treatment strategies.

• Klíčová slova
• ABC transporters, CYP, Multidrug resistance, Pharmacokinetic interactions, Ribociclib,
• MeSH
• ABC transportér z rodiny G, člen 2 antagonisté a inhibitory   metabolismus   MeSH
• aminopyridiny farmakokinetika   MeSH
• buňky MDCK MeSH
• inhibitory cytochromu P450 farmakokinetika   MeSH
• izoenzymy antagonisté a inhibitory   metabolismus   MeSH
• lékové interakce fyziologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• P-glykoproteiny antagonisté a inhibitory   metabolismus   MeSH
• psi MeSH
• puriny farmakokinetika   MeSH
• substrátová specifita účinky léků   fyziologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportér z rodiny G, člen 2 MeSH
• ABCB1 protein, human MeSH Prohlížeč
• ABCG2 protein, human MeSH Prohlížeč
• aminopyridiny MeSH
• inhibitory cytochromu P450 MeSH
• izoenzymy MeSH
• nádorové proteiny MeSH
• P-glykoproteiny MeSH
• puriny MeSH
• ribociclib MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH

Ten Enterobacteriaceae isolates collected in a Czech hospital carried blaKPC-positive plasmids of different sizes (∼30, ∼45, and ∼80 kb). Sequencing revealed three types of plasmids (A to C) with the Tn4401a transposon. Type A plasmids comprised an IncR backbone and a KPC-2-encoding multidrug resistance (MDR) region. Type B plasmids were derivatives of type A plasmids carrying an IncN3-like segment, while type C plasmids were IncP6 plasmids sharing the same KPC-2-encoding MDR region with type A and B plasmids.

• Klíčová slova
• Citrobacter freundii, Illumina sequencing, IncR, ST18, Tn4401a,
• MeSH
• antibakteriální látky terapeutické užití   MeSH
• beta-laktamasy genetika   metabolismus   MeSH
• Citrobacter freundii účinky léků   enzymologie   genetika   izolace a purifikace   MeSH
• enterobakteriální infekce farmakoterapie   epidemiologie   mikrobiologie   MeSH
• Escherichia coli účinky léků   enzymologie   genetika   izolace a purifikace   MeSH
• exprese genu MeSH
• izoenzymy genetika   metabolismus   MeSH
• karbapenemy terapeutické užití   MeSH
• Klebsiella pneumoniae účinky léků   enzymologie   genetika   izolace a purifikace   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence genetika   MeSH
• Morganella morganii účinky léků   enzymologie   genetika   izolace a purifikace   MeSH
• nemocnice MeSH
• otevřené čtecí rámce MeSH
• plazmidy chemie   klasifikace   metabolismus   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• transpozibilní elementy DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antibakteriální látky MeSH
• beta-lactamase KPC-2 MeSH Prohlížeč
• beta-laktamasy MeSH
• izoenzymy MeSH
• karbapenemy MeSH
• transpozibilní elementy DNA MeSH

Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular mechanisms of their action are now fairly well understood. However, little attention has been paid to naturally occurring alternative isoforms of chromatin modifying proteins and to their biological roles. In this review, we focus on mammalian KDM2A and KDM2B, the only two lysine demethylases whose genes have been described to produce also an alternative isoform lacking the N-terminal demethylase domain. These short KDM2A/B-SF isoforms arise through alternative promoter usage and seem to play important roles in development and disease. We hypothesise about the biological significance of these alternative isoforms, which might represent a more common evolutionarily conserved regulatory mechanism.

• Klíčová slova
• KDM2A; KDM2B; lysine demethylase; epigenetics; chromatin; alternative isoform; alternative promoter,
• MeSH
• izoenzymy nedostatek   genetika   metabolismus   MeSH
• Jumonjiho doména s histondemethylasami nedostatek   genetika   metabolismus   MeSH
• lidé MeSH
• nádory enzymologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• izoenzymy MeSH
• Jumonjiho doména s histondemethylasami MeSH