KAMISAKO, T. and OGAWA, H. (2005), Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis. Journal of Gastroenterology and Hepatology, 20: 1429-1434. doi: 10.1111/j.1440-1746.2005.03950.x ...
Title: Structure and Function of the Human Breast Cancer Resistance Protein (BCRP/ABCG2). VOLUME: 11 ISSUE: 7. Author(s):Zhanglin Ni, Zsolt Bikadi, Mark F. Rosenberg and Qingcheng Mao. Affiliation:Department of Pharmaceutics,School of Pharmacy, University of Washington, Health Science Building H272, 1959 NE Pacific Street , Seattle, Washington 98195-7610, USA.. Keywords:Breast cancer resistance protein, BCRP, ATP-binding cassette transporter, ABCG2, multidrug resistance, drug disposition, homology model, mutation analysis, BCRP/ABCG2, mitoxantrone-resistant human cancer cell lines, MXR, human placenta, ABCP, nucleotide binding domains, membrane spanning domains, MSDs, affinity constants, SAR, QSAR, flavonoids, tamoxifen analogues, cyclindependent kinase inhibitors, tariquidar analogues, FTC analogues, 2D-QSAR, CoMFA, CoMSIA, 3D-QSAR, MIFs, HEK cells, Pichia pastoris, Lactococcus lactis, fluorescence resonance energy transfer v, MODELLER. Abstract: The human breast cancer resistance protein ...
ABCC4 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), transcript variant 2 - 10 µg - OriGene - cdna clones
TY - JOUR. T1 - A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. AU - Zhang, Kang. AU - Garibaldi, Daniel C.. AU - Kniazeva, Marina. AU - Albini, Thomas. AU - Chiang, Michael F.. AU - Kerrigan, Michelle. AU - Sunness, Janet S.. AU - Han, Min. AU - Allikmets, Rando. PY - 1999/12/1. Y1 - 1999/12/1. N2 - PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a ...
Overexpression of adenosine triphosphate-binding cassette (ABC) transport proteins is emerging seeing that a crucial contributor to anticancer medication level of resistance. assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it had been demonstrated that eIF4G and ABC translation protein were downregulated in MCF-7/ADR cells after transfection with miR-503 significantly. It was discovered that miR-503 mimics could sensitize the cells to treatment with ADM, TAX and TAM. These findings confirmed for the very first time that eIF4G acted as an integral element in MCF-7/ADR cells, and Riociguat could end up being a competent agent for preventing and reversing multi-drug resistance in breast malignancy. (11) determinded that cisplatin-resistance cells upregulated MRP1 when compared with sensitive MCF-7 cells. The eukaryotic initiation factor (eIF) 4F complex consists of three proteins: cap-binding protein eIF4E, scaffolding protein eIF4G and ...
Title: Genetic Polymorphisms of ATP-Binding Cassette Transporters ABCB1 and ABCC2 and their Impact on Drug Disposition. VOLUME: 12 ISSUE: 5. Author(s):Vincent Haufroid. Affiliation:Laboratory of Analytical Chemistry, Saint-Luc Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium.. Keywords:Pharmacogenomics, ABCB1, ABCC2, intracellular concentrations, genotype, polymorphism, mdr1, mrp2, drug disposition, haplotypes. Abstract: The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes, and act as efflux proteins. ABC transporters are characterised by the presence of genetic polymorphisms mainly represented by single nucleotide polymorphisms (SNPs), some of which having an impact on their activity. Besides physiological substances, drugs are also substrates of some ABC transporters, mainly ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2. Identifying the impact of these polymorphisms on the ...
During the past years, we and others discovered a series of human ATP-binding cassette (ABC) transporters, now referred to as ABC A-subfamily transporters. Recently, a novel testis-specific ABC A transporter, Abca17, has been cloned in rodent. In this study, we report the identification and characterization of the human ortholog of rodent Abca17. The novel human ABC A-transporter gene on chromosome 16p13.3 is ubiquitously expressed with highest expression in glandular tissues and the heart. The new ABC transporter gene exhibits striking nucleotide sequence homology with the recently cloned mouse (58%) and rat Abca17 (51%), respectively, and is located in the syntenic region of mouse Abca17 indicating that it represents the human ortholog of rodent Abca17. However, unlike in the mouse, the full-length ABCA17 transcript (4.3 kb) contains numerous mutations that preclude its translation into a bona fide ABC transporter protein strongly suggesting that the human ABCA17 gene is a transcribed pseudogene
[51 Pages Report] Check for Discount on ATP Binding Cassette Sub Family A Member 1 (ATP Binding Cassette Transporter 1 or ABC 1 or ATP Binding Cassette 1 or Cholesterol Efflux Regulatory Protein or ABCA1) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, ATP Binding Cassette Sub...
ATP-binding cassette transporters (ABC transporters) are members of a transport system superfamily that is one of the largest and is possibly one of the oldest families with representatives in all extant phyla from prokaryotes to humans. ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate. Most but not all uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair. ABC transporters are considered to be with the ABC superfamily based on the sequence and organization of their ATP-binding cassette (ABC) domains, even though the integral membrane proteins ...
With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al.). Now, Najafi-Shoushtari et al. (p. 1566, published online 13 May) and Rayner et al. (p. 1570, published online 13 May) have discovered a new molecular player in cholesterol control-a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element-binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate-binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or "good" cholesterol) and that helps to remove "bad" cholesterol from the blood. ...
With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al.). Now, Najafi-Shoushtari et al. and Rayner et al. have discovered a new molecular player in cholesterol control-a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element-binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate-binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or "good" cholesterol) and that helps to remove "bad" cholesterol from the blood. Reducing the levels of miR-33 in mice boosted serum HDL levels, ...
Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. At the onset of this thesis work, only a few structure-activity models, in general describing P-glycoprotein (Pgp/ABCB1) interactions, were developed using small datasets with little structural diversity. In this thesis, drug-transport protein interactions were explored using large, diverse datasets representing the chemical space of orally administered registered drugs. Focus was set on the ATP-binding cassette (ABC) transport proteins expressed in the canalicular membrane of human hepatocytes.. The inhibition of the ABC transport proteins multidrug-resistance associated protein 2 (MRP2/ABCC2) and bile salt export pump (BSEP/ABCB11) was experimentally investigated using membrane vesicles from cells overexpressing the investigated proteins and sandwich cultured human hepatocytes (SCHH). Several previously unknown inhibitors were identified for both of the proteins ...
TY - JOUR. T1 - ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population. T2 - Cross-sectional data from the Daiko study. AU - Mokuno, Junichiro. AU - Hishida, Asahi. AU - Morita, Emi. AU - Sasakabe, Tae. AU - Hattori, Yuta. AU - Suma, Shino. AU - Okada, Rieko. AU - Kawai, Sayo. AU - Naito, Mariko. AU - Wakai, Kenji. PY - 2015/4/11. Y1 - 2015/4/11. N2 - Among polymorphisms in ATP-binding cassette transporter Al (ABCA1) gene, the available evidence demonstrates that the ABCA1 R219K polymorphism (G1051A, rs2230806) K allele is associated with a higher high-density lipoprotein cholesterol (HDL- C) level and may play a protective role against coronary artery disease (CAD) risk in Asians and Caucasians. The findings from many underpowered studies from Asian countries (n=71-597), however, still remain inconsistent. The objective of this study was to overcome the limitations of previous ...
Introduction Recently, the ATP-binding cassette transporter BCRP1/ABCG2 has been shown to regulate the function and survival of side population cells, which have been identified in various organs including heart and have stem cell properties. In addition, previous studies have revealed that BCRP1/ABCG2 is also expressed in endothelial cells of capillaries and arterioles in heart. This study was performed to clarify the role of BCRP1/ABCG2 in cardiac repair after myocardial infarction (MI).. Methods and Results MI was induced in 8- to 12-week-old wild-type (WT) mice (n=51) and Bcrp1/Abcg2 knock-out (KO) mice (n=60) by ligating the left anterior descending artery. At 28 days after MI, the survival rate was significantly lower in KO mice than in WT mice (28.3% versus 74.5%, p=0.0001). The main cause of death in KO mice was cardiac rupture (CR) (67.4%), whereas CR was observed in only 30.8% among WT mice (p=0.019). Echocardiography showed that ventricular remodeling was more deteriorated in KO mice ...
ABCF3 - ABCF3 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family F (GCN20), member 3 (ABCF3) available for purchase from OriGene - Your Gene Company.
Purpose : The retina specific ATP binding cassette transporter A4 (ABCA4) is necessary for the clearance of all-trans-retinal from photoreceptor cells. Loss of this crucial function results in the accumulation of toxic bisretinoids, primarily N-retinylidene-N-retinylethanolamine (A2E). This ultimately leads to the Stargardt phenotype of increased autofluorescence and progressive RPE and photoreceptor cell loss. Adeno-associated virus (AAV) vectors have proven their utility for efficient gene transfer in the retina to a variety of cell types. However, the ABCA4 coding sequence (cds) of 6.8kb exceeds the payload capacity of a single AAV capsid of 4.8kb by far. AAV dual vectors have been shown to overcome this size restriction by splitting the cds between two vectors and packaging them in separate capsids. After co-infection of a cell the two vectored cDNAs recombine to reconstitute the full length cds. Here we present recent data on the effect of AAV dual vector mediated ABCA4 gene replacement ...
hypothetical protein, ABCB1LB, ATP-binding cassette, sub-family B (MDR/TAP), member 1-like B, A306_07528, ABC16, ABC member 16, MDR/TAP subfamily, AS27_06659, AS28_00614, ATP-binding cassette protein B11, ATP-binding cassette, sub-family B (MDR/TAP), member 11, ATP-binding cassette, subfamily B (MDR/TAP), member 11, ATP-binding cassette, sub-family B (MDR/TAP), member 11-like protein, ATP-binding cassette sub-family B member 11, ATP-binding cassette, sub-family B, member 11, bile salt export pump, BRIC2, BSEP, BSEP/SPGP, CB1_000638007, D623_10034923, GW7_06212, H920_16172, I79_001236, Lith1, liver bile salt export pump, M91_01875, M959_07155, MDA_GLEAN10024246, Multidrug resistance protein 1, N301_03105, N302_06788, N303_07198, N305_06591, N306_04080, N307_07545, N308_11810, N309_07944, N312_11735, N321_13718, N327_01303, N328_07355, N329_09470, N331_01374, N332_02914, N333_01536, N334_13094, N336_04014, N340_01262, N341_10800, PAL_GLEAN10025937, PFIC2, PFIC-2, PGY4, progressive familial ...
Wholesale Human Transporter ☆ Find 1,504 human transporter products from 673 manufacturers & suppliers at EC21. ☆ Choose quality human transporter manufacturers, suppliers & exporters now - EC21
The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cellular unesterified cholesterol and phospholipid to lipid-poor apolipoprotein A-I. Chymase, a protease secreted by mast cells, selectively cleaves pre-β-migrating particles from high density lipoprotein (HDL)3 and reduces the efflux of cholesterol from macrophages. To evaluate whether this effect is the result of reduction of ABCA1-dependent or -independent pathways of cholesterol efflux, in this study we examined the efflux of cholesterol to preparations of chymase-treated HDL3 in two types of cell: 1) in J774 murine macrophages endogenously expressing low levels of scavenger receptor class B, type I (SR-BI), and high levels of ABCA1 upon treatment with cAMP; and 2) in Fu5AH rat hepatoma cells endogenously expressing high levels of the SR-BI and low levels of ABCA1. Treatment of HDL3 with the human chymase resulted in rapid depletion of pre-β-HDL and a concomitant decrease in the efflux of cholesterol and phospholipid ...
ABCA12 - ABCA12 (Myc-DDK-tagged)-Human ATP-binding cassette, sub-family A (ABC1), member 12 (ABCA12), transcript variant 2 available for purchase from OriGene - Your Gene Company.
Cholesterol is an essential molecule that mediates a myriad of critical cellular processes, such as signal transduction in eukaryotes, membrane fluidity, and steroidogenesis. As such it is not surprising that cholesterol homeostasis is tightly regulated, striking a precise balance between endogenous synthesis and regulated uptake/efflux to and from extracellular acceptors. In mammalian cells, sterol efflux is a key component of the homeostatic equation and is mediated by members of the ATP binding cassette (ABC) transporter superfamily. ATP-binding cassette (ABC) transporters represent a group of evolutionarily highly conserved cellular transmembrane proteins that mediate the ATP-dependent translocation of substrates across membranes. Members of this superfamily, ABCA1 and ABCG1, are key components of the reverse cholesterol transport pathway. ABCG1 acts in concert with ABCA1 to maximize the removal of excess cholesterol from cells by promoting cholesterol efflux onto mature and nascent HDL particles
S. griseus mutant NP4, which was isolated by UV mutagenesis, showed a bald and wrinkled colony morphology because of ectopic septation in substrate hyphae and subsequent spore formation. The ectopic spores were the same as aerial spores in size, thickness of the spore wall, and shape, as determined by transmission and scanning electron microscopy, and in heat and lysozyme susceptibility. Mutant NP4 also formed abundant spores in liquid medium, whereas the parental strain IFO13350 rarely forms submerged spores under these conditions. The wall of the ectopic spores is supposed to be thicker than those of the submerged spores formed by several Streptomyces spp., including S. griseus B-2682 (32), under specific conditions, because the spores of NP4 were resistant to lysozyme. We therefore assume that both on solid and in liquid medium, mutant NP4 forms two separate cross walls in the vegetative hyphae and matures each compartment into a spore indistinguishable from aerial spores in many aspects, as ...
Active drug efflux by the adenosine triphosphate-binding cassette (ABC) transporter ABCG2 is one of the common mechanisms causing multiple drug resistance in various human cancers. In the intrinsic drug resistance of hepatocellular carcinoma (HCC), the role of ABCG2 is closely associated with side population (SP), a minor subset of cancer stem-like cells with unique capacity to extrude lipophilic dye Hoechst 33342 and many chemotherapeutic agents. In this study, we showed that ABCG2 was intrinsically expressed in a subgroup of HCC tissues and its expression pattern significantly influenced the levels of drug efflux from HCC cell lines. In MHCC-97L HCC cell line with intrinsic ABCG2 expression, we confirmed the importance of SP cells to the drug efflux-related chemotherapy resistance and found that the SP analysis provided an efficient method to evaluate the functional activity of ABCG2 transporter. In this cell line, we discovered that the SP proportion was modulated by the treatments of Akt ...
ATP binding cassette (ABC) transporters mediate vital transport processes in every living cell. ATP hydrolysis, which fuels transport, displays positive cooperativity in numerous ABC transporters. In particular, heterodimeric ABC exporters exhibit pronounced allosteric coupling between a catalytically impaired degenerate site, where nucleotides bind tightly, and a consensus site, at which ATP is hydrolyzed in every transport cycle. Whereas the functional phenomenon of cooperativity is well described, its structural basis remains poorly understood. Here, we present the apo structure of the heterodimeric ABC exporter TM287/288 and compare it to the previously solved structure with adenosine 5-(β,γ-imido)triphosphate (AMP-PNP) bound at the degenerate site. In contrast to other ABC exporter structures, the nucleotide binding domains (NBDs) of TM287/288 remain in molecular contact even in the absence of nucleotides, and the arrangement of the transmembrane domains (TMDs) is not influenced by ...
Mouse Monoclonal Anti-ABCD3 Antibody against Human ATP-binding cassette, sub-family D (ALD), member 3. Validated for Immunofluorescence and Immunohistochemistry
Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP) cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC) drug transport protein family, such as ABCG2 and ABCA3. Using ...
Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules. The TAP structure is formed of two proteins: TAP-1 and TAP-2, which have one hydrophobic region and one ATP-binding region each. They assemble into a heterodimer, which results in a four-domain transporter. The TAP transporter is found in the ER lumen associated with the peptide-loading complex (PLC). This complex of β2 microglobulin, calreticulin, ERp57, TAP, tapasin, and MHC class I acts to keep hold of MHC molecules until they have been fully loaded with peptides. TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. Association with TAP is an ATP-independent event, in a fast bimolecular association step, peptide binds to TAP, followed by a slow isomerisation of the TAP complex. It is suggested that the ...
Human Transporter Database: Comprehensive Knowledge and Discovery Tools in the Human Transporter Genes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
TY - JOUR. T1 - Drug efflux by breast cancer resistance protein is a mechanism of resistance to the benzimidazole insulin-like growth factor receptor/insulin receptor inhibitor, BMS-536924. AU - Hou, Xiaonan. AU - Huang, Fei. AU - Carboni, Joan M.. AU - Flatten, Karen. AU - Asmann, Yan. AU - Ten Eyck, Cynthia. AU - Nakanishi, Takeo. AU - Tibodeau, Jennifer D.. AU - Ross, Douglas D.. AU - Gottardis, Marco M.. AU - Erlichman, Charles. AU - Kaufmann, Scott H. AU - Haluska, Paul. PY - 2011/1. Y1 - 2011/1. N2 - Preclinical investigations have identified insulin-like growth factor (IGF) signaling as a key mechanism for cancer growth and resistance to clinically useful therapies in multiple tumor types including breast cancer. Thus, agents targeting and blocking IGF signaling have promise in the treatment of solid tumors. To identify possible mechanisms of resistance to blocking the IGF pathway, we generated a cell line that was resistant to the IGF-1R/InsR benzimidazole inhibitors, BMS-554417 and ...
Background: Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin (p28, p28GANK or PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/ MX) and non-MDR counterparts (MCF-7). Methods: Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2 (also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR. Western blot analysis was used to detect the protein expression levels of Gankyrin. Results: The PCR results showed that the expression of Gankyrin was significantly lower in the ABCG2 overexpressing cell line MCF-7/MX than in non-resistanct MCF-7 cells. In contrast, there were no significant differences in mRNA expression of Gankyrin in the MDR1 overexpressing cell line MCF-7/ADR in comparison with MCF-7 cells. Similarly,
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Multidrug resistance protein 1 (MRP1) is a member of the "C" branch of the ATP-binding cassette transporter superfamily. The NH2-proximal nucleotide-binding domain (NBD1) of MRP1 differs functionally from its COOH-proximal domain (NBD2). NBD1 displays intrinsic high-affinity ATP binding and little ATPase activity. In contrast, ATP binding to NBD2 is strongly dependent on nucleotide binding by NBD1, and NBD2 is more hydrolytically active. We have demonstrated that occupancy of NBD2 by ATP or ADP markedly decreased substrate binding by MRP1. We have further explored the relationship between nucleotide and substrate binding by examining the effects of various ATP analogs and ADP trapping, as well as mutations in conserved functional elements in the NBDs, on the ability of MRP1 to bind the photoactivatable, high-affinity substrate cysteinyl leukotriene C4 (LTC4). Overall, the results support a model in which occupancy of both NBD1 and NBD2 by ATP results in the formation of a low-affinity ...
SUR1 is an ATP-binding cassette (ABC) transporter with a novel function. In contrast to other ABC proteins, it serves as the regulatory subunit of an ion channel. The ATP-sensitive (KATP) channel is an octameric complex of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits, and it links cell metabolism to electrical activity in many cell types. ATPase activity at the nucleotide-binding domains of SUR results in an increase in KATP channel open probability. Conversely, ATP binding to Kir6.2 closes the channel. Metabolic regulation is achieved by the balance between these two opposing effects. Precisely how SUR1 talks to Kir6.2 remains unclear, but recent studies have identified some residues and domains that are involved in both physical and functional interactions between the two proteins. The importance of these interactions is exemplified by the fact that impaired regulation of Kir6.2 by SUR1 results in human disease, with loss-of-function SUR1 mutations causing congenital
Axon Medchem | Prime source supplier of high-value life science products, providing Axon Ligands™ for pharmaceutical research as world-wide recognized drug standards
Discussion. In this work, we describe a patient presenting typical STGD due to mutations in the ABCA4 gene. This gene encodes the ABCA4 protein, a member of the ATP-binding cassette transporters superfamily. It is involved in the transport of vitamin A derivatives across the membrane of the outer segment discs of photoreceptors [18,19].. In this affected woman, the homozygous p.Arg1129Leu mutation was identified. The inheritance pattern of the disease-associated alleles was not autosomal recessive as usual. Heterozygosity for the mutation was only detected in her father. Assumed paternity was confirmed by different STR markers [20]; therefore the proband either had (partial) paternal isodisomy for chromosome 1 or an unbalanced karyotype due to maternal microdeletion involving chromosome 1p, leading to hemizygosity for the ABCA4 locus. Both standard and HR karyotypes were normal, which excluded major structural chromosomal abnormalities. Dosage analysis performed by MLPA confirmed the presence of ...
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily which uses the hydrolysis of ATP to energize diverse biological import and export systems (see ,PDOC00185,). ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) [1,2,3]. The function of the integral inner-membrane protein is to translocate the substrate across the membrane. Studies of P-glycoprotein function indicate that residues lining the proposed chamber opening (residues of TM2, TM5 and TM6) play an important role in substrate recognition [4]. In exporters and eukaryotes, ABC transporters consist of a single polypeptide composed of an N-terminal domain of approximately 320 residues, apparently containing six transmembrane segments, fused to a highly conserved ...
ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from peripheral cells to HDL particles, which transport cholesterol to liver for processing for excretion. ABCG1, and not ABCA1, was found to be critical for the proliferation of T lymphocytes. Despite this, to date, very little is known about the role of ABCG1 in T cells during atherogenesis. In this study, we aim to understand how ABCG1 regulates T cell function and how absence of ABCG1 selectively in T cells impacts atherosclerosis. We found that, on a high cholesterol diet, mice with T cell-specific ABCG1 deficiency on the LDLR-/- background (LCK-Cre+/ABCG1fl/fl/LDLR-/-) developed 40% less atherosclerotic lesions than their littermate controls (LCK-Cre-/ABCG1fl/fl/LDLR-/-) (P,0.0001). Furthermore, we found that the percentage of CD4+CD25+Foxp3+ regulatory T cells was increased in the LCK-Cre+/ABCG1fl/fl/LDLR-/- mice compared to the littermate controls (P,0.01). Since Tregs are considered anti-atherogenic, we hypothesize ...
Purified Recombinant Human ABCG2, GST-tagged from Creative Biomart. Recombinant Human ABCG2, GST-tagged can be used for research.
TY - JOUR. T1 - Changes in corneal basal epithelial phenotypes in an altered basement membrane. AU - Wang, I. Jong. AU - Tsai, Jui-Fang. AU - Yeh, Lung Kun. AU - Tsai, Ryan Yao Nien. AU - Hu, Fung Rong. AU - Kao, Winston W Y. PY - 2011. Y1 - 2011. N2 - Background: To examine the corneal epithelial phenotype in an altered basement membrane. Methodology/Principal Findings: Corneas from 9 patients with symptoms of continuous unstable corneal curvature (CUCC) were harvested by penetrating keratoplasty and subjected to histology examination and immunohistochemical staining with transactivating and N-terminally truncated pP63 transcript (DNp63), cytokeratin 3 (Krt3), ATP-binding cassette subfamily G member 2 (ABCG2), connexin 43 (CX43), p38 mitogen-activated protein kinases (p38MAPK), activating protein 2 (TFAP2), and extracellular signal-regulated kinase (Erk1/2) monoclonal antibodies. Positive immunostaining with ABCG2, p38MAPK, and TFAP2 monoclonal antibodies was observed in the basal epithelial ...
Transporters for Glucocorticoids: Exploring a New Paradigm for Steroid Hormone Regulation and a Potential Strategy for Identification of Toxin/Disruptor Transporter Machineries A well-entrenched paradigm holds that steroid hormones, like glucocorticoids (GCs), diffuse freely across plasma membranes in order to access their intracellular receptors and influence gene transcription. This view persists despite biochemical, genetic, and cell biological evidence, albeit sporadic, consistent with mediated transport (herein referred to as any process that moves molecules across plasma membranes, including active transport, endocytosis/pinocytosis, passage through pores or channels, and/or coupling to carrier proteins) of steroids. Nearly two decades ago, for example, we identified a conserved ATP-binding-cassette transporter that selectively exports dex in yeast, and showed that a drug that inhibits the yeast activity also leads to increased intracellular dex in mammalian cells. Nevertheless, the widely ...
The peroxisomal ABC-transporters Pxa1p and Pxa2p are half transporters. Previous genetic investigations have demonstrated that Pxa1p and Pxa2p have to dimerise in order to build a functional transporter, which is very likely involved in the import of long chain fatty acids into peroxisomes of S. cerevisiae. In this work, tagged versions of the proteins were purified as a complex. This proved for the building of a stable hetero dimer. For characterisation of the ATP binding properties, the transporters were incubated and cross linked with 8-azido-[alpha-32P]-ATP. This revealed an asymmetric binding of the ATP analogue. Pxa2p binds much more azido-ATP, than Pxa1p, while the dissociation constants are rather similar. The poorer ATP binding of Pxa1p is reflected by degenerated sequence motifs in the nucleotide binding fold. The purified ABC-transporters have been used for ATPase assays. They showed a basal ATPase activity, which could be stimulated by addition of long chain fatty acid CoAs, like ...
The release of substrate into the translocation pathway of an ABC transporter is undoubtedly coupled to conformational changes in the binding protein (5, 7). In the absence of transporter, binding proteins such as the maltose binding protein (MBP) exhibit large hinge and twist movements of one lobe relative to the other between the liganded and unliganded states (7). In contrast, binding proteins such as BtuF and FhuD with a backbone α-helix are thought to be less likely to undergo such motions (18-20). Recently, the structure of one such binding protein, T. pallidum TroA, was solved with (19) and without (26) bound Zn2+. The difference between liganded and unliganded TroA was indeed found to be a mere 4° tilting of the C-terminal domain about the long axis of the protein without bending or unwinding of the backbone helix. This movement is very different from that observed for MBP and yet the result is a partial collapse of the binding site and the loss of the proper coordination geometry for ...
Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance(MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins(MRP1, MRP2) and breast cancer resistance protein(BCRP). Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective and promising platforms for treatment of drug resistant cancer cells. Nanocarriers have potential to improve drug therapeutic index, ability for multifunctionality, divert ABC-transporter mediated drug efflux mechanism and selective targeting to tumor cells, cancer stem cells, tumor initiating cells or cancer microenvironment. Selective
UNLABELLED: Breast cancer resistance protein (BCRP, ABCG2) is a xenobiotic half-transporter protein. It is a member of the ATP-binding cassette protein family and functions as an energy-dependent efflux pump. BCRP is involved in multidrug resistance. The study aimed at examining BCRP expression in breast cancers and at defining a relationship between activity of this protein and clinical course of the cancer. MATERIALS AND METHODS: We analyzed the expression of BCRP in 101 stage II breast cancer patients. All the patients were diagnosed and treated at the Lower Silesia Oncology Centre (LSOC) between January 1993 and June 1994. After the treatment the patients remained under constant control at LSOC. Mean duration of the observation was 14.2 years (ranging between 9.1 and 16.5 years). Data related to relapse of the disease and deaths were obtained from medical documentation stored in LSOC. The immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
We have analyzed the normal human tissue distribution of BCRP using a recently developed Mab BXP34 (10) and a newly developed Mab BXP-21. Both Mabs show pronounced staining at the plasma membrane of BCRP-overexpressing tumor cell lines. In contrast to BXP-34, BXP-21 is also reactive on immunoblots, yielding a protein band of approximately Mr 72,000, the expected size of BCRP. BXP-21 did not cross-react with other MDR transporters like P-gp, MRP1, and MRP2. In the Western blotting and immunoprecipitation experiments, BCRP was found to be differentially glycosylated in T8 and MX3 tumor cells. Whether this difference in glycosylation reflects differences in BCRP functioning remains to be investigated.. From previously reported mRNA data (1 , 4) , BCRP is known to be highly expressed in the placenta and at lower levels in the liver, small intestine, colon, and ovary. In one study (4) , low expression of BCRP was observed in the kidney and heart as well. Using semiquantitative RT-PCR, we confirmed ...
The protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily and is expressed predominantly in liver tissue. The function has not yet been determined but may involve cholesterol transport. Alternate splice variants have been described but their full length sequences have not been determined. [provided by RefSeq, Jul 2008 ...
Notably, under conditions in which no killing of cells occurred, exposure of yeast over hundreds of generations to increasing concentrations of AmB has yielded resistant strains with permanent changes in the expression of genes such as yor1 and pdr16 (41), which are members of the ATP-binding cassette (ABC) family of transporters (9). The activation of yor1 and pdr16 is controlled by the zinc finger transcription factors Pdr1 and Pdr3, which activate proteins involved in multidrug resistance and in the translocation of plasma membrane phospholipids (9). Among the stably overexpressed genes that also confer resistance to AmB (41) are ict1, which encodes a lysophosphatidic acid acyltransferase that is responsible for enhanced phospholipid synthesis and increased resistance to antifungal drugs, and ygr035C and ypl088, which are activated by Yrm1q and Yrr1, the yeast zinc finger transcription factors which are also controlled by the pleiotropic drug resistance (PDR) gene network (9).. Another yeast ...