Disease relevance of MARCKSL1

• We tested the novel MLP1 polymorphism and the MACS flanking markers in a series of 43 Caucasian simplex families in which the affected child had a lumbosacral myelomeningocele [1].
• Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines [2].
• Using an RNase protection assay we have analyzed the expression of MRP in non-Pgp MDR sublines of the human lung cancer cell lines SW-1573 (non-small cell lung cancer) and GLC4 (small cell lung cancer) [2].
• The aim of this clinical study was to evaluate whether (99m)Tc-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and (99m)Tc-MIBI imaging to predict the clinical outcome [3].
• The glioma cell lines were the two MRP-expressing cell lines, T98G and IN500, an MDR1-expressing cell line, CCF-STTG1, and the MRP1 MDR1-non-expressing cell line, IN157 [4].

Psychiatry related information on MARCKSL1

• Movement-related potentials (MRP) and reaction times (RT) were recorded from 10 healthy subjects during blocks of unimanual visuomotor trials before and after a bimanual training task [5].
• The traditional averaging techniques to obtain the slow-wave movement-related potentials (MRP) and Morlet wavelet transform to obtain EEG time-frequency (TF) profiles associated with task performance were used [6].

High impact information on MARCKSL1

• One of these CCAAT-binding proteins, CP1, binds with high affinity to CCAAT elements present in the human alpha-globin promoter and the adenovirus major late promoter (MLP) [7].
• How does the MRP/GS-X pump export doxorubicin [8]?
• Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, including dendritic spines of neurons [9].
• We have previously shown that the multi-drug resistance protein (MRP) mediates the ATP-dependent membrane transport of glutathione S-conjugates and additional amphiphilic organic anions [10].
• In the present study we demonstrate the expression of MRP in hepatocytes where it functions in hepatobiliary excretion [10].

Chemical compound and disease context of MARCKSL1

• In addition, the MLP could be cis-activated by the BK virus enhancer in both human and monkey kidney cells; approximately 20 times more chloramphenicol acetyltransferase was produced from expression vectors containing a hybrid promoter (BL), in which the BK enhancer was upstream of the MLP, than from expression vectors containing the MLP alone [11].
• The function of guanosine residues surrounding the TATA box of the adenovirus 2 major late promoter (MLP) in promoting efficient transcription initiation and in selecting a specific transcription start site in vitro has been examined [12].
• During the MLP, RU486-induced uterine bleeding occurred in all 10 women 36-72 h after the first dose [13].
• In vitro experiments with rat (II-45) and human (MERO 25) mesothelioma cell lines revealed that the CMV promoter was stronger than the MLP promoter regarding levels of expression of the luciferase reporter gene and ganciclovir (GCV) killing efficiency after tk gene transfer [14].
• We examined the cytotoxicity, biochemical effects and metabolism of 4-methoxy-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP), a synthetic nucleoside inhibitor of phosphoribosylpyrophosphate synthetase, in HCT 116 human colorectal cancer cells [15].

Biological context of MARCKSL1

• The transporter proteins MRP and TAP are both members of the adenosine triphosphate (ATP)-binding cassette (ABC) family of transmembrane transporters, but each has distinct differences in substrate specificity [16].
• TopoIIalpha and MRP gene expression showed no significant changes [17].
• However, how dynamitin is involved in cell adhesion is unclear despite the fact that both MacMARCKS and microtubules regulate beta(2) integrin activation [18].
• In vivo interaction between dynamitin and MacMARCKS detected by the fluorescent resonance energy transfer method [19].
• The multidrug resistance (+associated) protein (MRP) is one of two ATP-dependent transport molecules which have been shown to be a cause of multidrug resistance in mammalian cells [20].

Anatomical context of MARCKSL1

• Disrupting the interaction with a short peptide derived from the MacMARCKS-binding domain of dynamitin caused macrophages to spread and flatten [21].
• MacMARCKS and dynamitin also partially colocalized at peripheral regions of macrophages and in the cell-cell border of 293 epithelial cells [21].
• In addition to MRP, the contents of mRNA coding for mdr-1, GST-pi, and topoisomerase II in the MDR sublines were higher than in the native cell line [22].
• Interestingly, GF120918 (1muM) did not abolish the polarized transport of digoxin in rat jejunum and ileum, and DIDS (0.5mM), not a P-gp inhibitor, and MK571 (50muM), an MRP-selective inhibitor, can also significantly decrease the exsorptive permeability of digoxin [23].
• There was an increase in MDR and MRP expression in Caco-2 cells after the acute treatment (1.5, 3, and 6 h) with venlafaxine [24].

Associations of MARCKSL1 with chemical compounds

• We report that dynamitin is a Ca(2+)/calmodulin-binding protein and that dynamitin binds directly to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS), a membrane-associated PKC substrate involved in macrophage spreading and integrin activation [21].
• For evaluation of the expression of MDR-related protein (MRP), mdr-1, glutathione transferase (GST-pi), and topoisomerase II mRNAs, the reverse transcription-polymerase chain reaction was used [22].
• Dynamitin, a subunit of the microtubule-dependent motor complex, was implicated in cell adhesion by binding to MacMARCKS (Macrophage-enriched myristoylated alanine-rice C kinase substrate) [18].
• In contrast, MRP inhibitors MK-571 and leukotriene C4 did not affect transport of paeoniflorin [25].
• In addition to a range of neutral or cationic cytotoxic drugs, MRP also transports heavy metals and organic anions including glutathione (GSH)-conjugates and glucuronate conjugates [20].

Physical interactions of MARCKSL1

• MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates G protein-mediated constitutive inhibition of calcium channels [26].

Regulatory relationships of MARCKSL1

• Concomitant with the inhibition of macrophage spreading and rosette formation, MacMARCKS mutant also inhibits integrin-dependent tyrosine phosphorylation of paxillin [27].

Other interactions of MARCKSL1

• These data suggest that the dynamitin-MacMARCKS interaction is involved in cell spreading [21].
• These include the MDR-related protein (MRP), the lung-resistance protein (LRP), and the transporter of antigenic peptides (TAP) [16].
• Calmodulin-binding was inhibited by phosphorylation of beta-adducin and of a MARCKS-related domain peptide by PKA and PKC [28].
• Regulation of MARCKS and MARCKS-related protein expression in BV-2 microglial cells in response to lipopolysaccharide [29].
• OBJECTIVE: To determine if the inflammatory cytokine macrophage inflammatory protein-1 alpha (MLP-1 alpha) stimulates the production of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) by human gestational tissues [30].

Analytical, diagnostic and therapeutic context of MARCKSL1

• RNA was isolated from the cells, and MDR and MRP genes were amplified using PCR [24].
• The cross-resistance to the natural product category drugs was found not to be mediated by the products of either the multidrug resistance 1 (MDR1) or multidrug resistance-associated protein (MRP) genes based on lack of coordinate increased expression or amplification of these genes as assessed by Northern and Southern blot analyses [31].
• A specific and quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay was developed for measuring the mRNA of the multidrug resistance-associated protein (MRP) [32].
• Double immunofluorescence microscopy and confocal laser scanning microscopy showed the presence of human MRP and rat Mrp in the canalicular as well as in the lateral membrane domains of hepatocytes [10].
• Similar complexes were observed when electrophoretic mobility shift assays of labeled MLP oligonucleotide were performed with rat liver nuclear extracts [33].

References