Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities.

Abstract:

:We report the cloning and functional analysis of a complete clone for the third member of the mouse mdr gene family, mdr3. Nucleotide and predicted amino acid sequence analyses showed that the three mouse mdr genes encode highly homologous membrane glycoproteins, which share the same length (1,276 residues), the same predicted functional domains, and overall structural arrangement. Regions of divergence among the three proteins are concentrated in discrete segments of the predicted polypeptides. Sequence comparison indicated that the three mouse mdr genes were created from a common ancestor by two independent gene duplication events, the most recent one producing mdr1 and mdr3. When transfected and overexpressed in otherwise drug-sensitive cells, the mdr3 gene, like mdr1 and unlike mdr2, conferred multidrug resistance to these cells. In independently derived transfected cell clones expressing similar amounts of either MDR1 or MDR3 protein, the drug resistance profile conferred by mdr3 was distinct from that conferred by mdr1. Cells transfected with and expressing MDR1 showed a marked 7- to 10-fold preferential resistance to colchicine and Adriamycin compared with cells expressing equivalent amounts of MDR3. Conversely, cells transfected with and expressing MDR3 showed a two- to threefold preferential resistance to actinomycin D over their cellular counterpart expressing MDR1. These results suggest that MDR1 and MDR3 are membrane-associated efflux pumps which, in multidrug-resistant cells and perhaps normal tissues, have overlapping but distinct substrate specificities.

journal_name

Mol Cell Biol

authors

Devault A,Gros P

doi

10.1128/mcb.10.4.1652

subject

Has Abstract

pub_date

1990-04-01 00:00:00

pages

1652-63

issue

4

eissn

0270-7306

issn

1098-5549

journal_volume

10

pub_type

杂志文章
  • Adenovirus origin of DNA replication: sequence requirements for replication in vitro.

    abstract::The initiation of adenovirus DNA takes place at the termini of the viral genome and requires the presence of specific nucleotide sequence elements. To define the sequence organization of the viral origin, we tested a large number of deletion, insertion, and base substitution mutants for their ability to support initia...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.2.864

    authors: Wides RJ,Challberg MD,Rawlins DR,Kelly TJ

    更新日期:1987-02-01 00:00:00

  • Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation.

    abstract::The cellular mechanisms involved in chronic inflammatory processes are poorly understood. This is especially true for the role of macrophages, which figure prominently in the inflammatory response. Two proteins, MRP8 and MRP14, which are expressed in infiltrate macrophages during inflammatory reactions but not in norm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.6.2402

    authors: Lagasse E,Clerc RG

    更新日期:1988-06-01 00:00:00

  • The N-terminal regulatory domain of Stp1p is modular and, fused to an artificial transcription factor, confers full Ssy1p-Ptr3p-Ssy5p sensor control.

    abstract::Stp1p and Stp2p are homologous and redundant transcription factors that are synthesized as latent cytoplasmic proteins with N-terminal regulatory domains. In response to extracellular amino acids, the plasma membrane-localized Ssy1p-Ptr3p-Ssy5p (SPS) sensor induces an endoproteolytic processing event that cleaves away...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.17.7503-7513.2004

    authors: Andréasson C,Ljungdahl PO

    更新日期:2004-09-01 00:00:00

  • Mutations in the yeast KEX2 gene cause a Vma(-)-like phenotype: a possible role for the Kex2 endoprotease in vacuolar acidification.

    abstract::Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.3.1534

    authors: Oluwatosin YE,Kane PM

    更新日期:1998-03-01 00:00:00

  • Components of the ESCRT pathway, DFG16, and YGR122w are required for Rim101 to act as a corepressor with Nrg1 at the negative regulatory element of the DIT1 gene of Saccharomyces cerevisiae.

    abstract::The divergently transcribed DIT1 and DIT2 genes of Saccharomyces cerevisiae, which belong to the mid-late class of sporulation-specific genes, are subject to Ssn6-Tup1-mediated repression in mitotic cells. The Ssn6-Tup1 complex, which is required for repression of diverse sets of coordinately regulated genes, is known...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.15.6772-6788.2005

    authors: Rothfels K,Tanny JC,Molnar E,Friesen H,Commisso C,Segall J

    更新日期:2005-08-01 00:00:00

  • A role for yeast and human translesion synthesis DNA polymerases in promoting replication through 3-methyl adenine.

    abstract::3-Methyl adenine (3meA), a minor-groove DNA lesion, presents a strong block to synthesis by replicative DNA polymerases (Pols). To elucidate the means by which replication through this DNA lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast Saccharomyces cerevisiae treated with the a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01079-07

    authors: Johnson RE,Yu SL,Prakash S,Prakash L

    更新日期:2007-10-01 00:00:00

  • The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.

    abstract::The CACCC-box binding protein erythroid Krüppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Krüppel-like factor, or KLF3. We have now tested the in vivo role of K...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00173-12

    authors: Funnell AP,Norton LJ,Mak KS,Burdach J,Artuz CM,Twine NA,Wilkins MR,Power CA,Hung TT,Perdomo J,Koh P,Bell-Anderson KS,Orkin SH,Fraser ST,Perkins AC,Pearson RC,Crossley M

    更新日期:2012-08-01 00:00:00

  • STAP-2 negatively regulates both canonical and noncanonical NF-kappaB activation induced by Epstein-Barr virus-derived latent membrane protein 1.

    abstract::The signal-transducing adaptor protein 2 (STAP-2) is a recently identified adaptor protein that contains a pleckstrin homology (PH) and Src homology 2 (SH2)-like domains, as well as a proline-rich domain in its C-terminal region. In previous studies, we demonstrated that STAP-2 binds to MyD88 and IKK-alpha or IKK-beta...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00194-08

    authors: Ikeda O,Sekine Y,Yasui T,Oritani K,Sugiyma K,Muromoto R,Ohbayashi N,Yoshimura A,Matsuda T

    更新日期:2008-08-01 00:00:00

  • Endogenous fluctuations of DNA topology in the chloroplast of Chlamydomonas reinhardtii.

    abstract::DNA supercoiling in the chloroplast of the unicellular green alga Chlamydomonas reinhardtii was found to change with a diurnal rhythm in cells growing in alternating 12-h dark-12-h light periods. Highest and lowest DNA superhelicities occurred at the beginning and towards the end of the 12-h light periods, respectivel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.12.7235

    authors: Salvador ML,Klein U,Bogorad L

    更新日期:1998-12-01 00:00:00

  • Fos and jun cooperate in transcriptional regulation via heterologous activation domains.

    abstract::The products of c-fos and c-jun (Fos and Jun) function in gene regulation by interacting with the AP-1 binding site. Here we have examined the contribution of Fos and Jun toward transcriptional activity by using Fos and Jun polypeptides purified from Escherichia coli. Fos contained a transcriptional activation domain ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.10.5532

    authors: Abate C,Luk D,Gagne E,Roeder RG,Curran T

    更新日期:1990-10-01 00:00:00

  • Differential regulation of transcription through distinct Suppressor of Hairless DNA binding site architectures during Notch signaling in proneural clusters.

    abstract::In Drosophila melanogaster, achaete (ac) and m8 are model basic helix-loop-helix activator (bHLH A) and repressor genes, respectively, that have the opposite cell expression pattern in proneural clusters during Notch signaling. Previous studies have shown that activation of m8 transcription in specific cells within pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00003-10

    authors: Cave JW,Xia L,Caudy M

    更新日期:2011-01-01 00:00:00

  • Cytoplasmic heat shock granules are formed from precursor particles and are associated with a specific set of mRNAs.

    abstract::In heat-shocked tomato cell cultures, cytoplasmic heat shock granules (HSGs) are tightly associated with a specific subset of mRNAs coding mainly for the untranslated control proteins. This messenger ribonucleoprotein complex was banded in a CsCl gradient after fixation with formaldehyde (approximately 1.30 g/cm3). It...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.3.1298

    authors: Nover L,Scharf KD,Neumann D

    更新日期:1989-03-01 00:00:00

  • Transformation of NIH 3T3 cells by overexpression of the normal coding sequence of the rat neu gene.

    abstract::While the normal human erbB-2 gene is potently transforming when overexpressed in NIH 3T3 cells, its rat homolog, the neu gene, seems to acquire transforming properties only upon alteration of its coding sequence. In this study, we compared the effects of different levels of expression of normal erbB-2 and neu in NIH ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.3247

    authors: Di Marco E,Pierce JH,Knicley CL,Di Fiore PP

    更新日期:1990-06-01 00:00:00

  • Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes.

    abstract::Transthyretin (TTR) and alpha 1-antitrypsin (alpha 1-AT) are expressed at high levels in the liver and also in at least one other cell type. We report here a detailed analysis of the proximal regulatory region of the TTR gene, which has uncovered two new DNA-binding factors that are present mainly (or only) in hepatoc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1415

    authors: Costa RH,Grayson DR,Darnell JE Jr

    更新日期:1989-04-01 00:00:00

  • Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.

    abstract::The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.1.427

    authors: Ucker DS,Wilson JD,Hebshi LD

    更新日期:1994-01-01 00:00:00

  • Overlapping functions of the pRb family in the regulation of rRNA synthesis.

    abstract::The "pocket" proteins pRb, p107, and p130 are a family of negative growth regulators. Previous studies have demonstrated that overexpression of pRb can repress transcription by RNA polymerase (Pol) I. To assess whether pRb performs this role under physiological conditions, we have examined pre-rRNA levels in cells fro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.21.17.5806-5814.2001

    authors: Ciarmatori S,Scott PH,Sutcliffe JE,McLees A,Alzuherri HM,Dannenberg JH,te Riele H,Grummt I,Voit R,White RJ

    更新日期:2001-09-01 00:00:00

  • Factors involved in specific transcription by mammalian RNA polymerase II: purification, genetic specificity, and TATA box-promoter interactions of TFIID.

    abstract::Selective and accurate transcription of purified genes by RNA polymerase II requires multiple factors. The factor designated TFIID was purified extensively from HeLa cell nuclear extracts by using a simple and novel complementation assay. Thus, TFIID was preferentially inactivated by mild heat treatment of a nuclear e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4028

    authors: Nakajima N,Horikoshi M,Roeder RG

    更新日期:1988-10-01 00:00:00

  • Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase.

    abstract::Protein sumoylation plays an important but poorly understood role in controlling genome integrity. In Saccharomyces cerevisiae, the Slx5-Slx8 SUMO-targeted Ub ligase appears to be needed to ubiquitinate sumoylated proteins that arise in the absence of the Sgs1 DNA helicase. WSS1, a high-copy-number suppressor of a mut...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01649-09

    authors: Mullen JR,Chen CF,Brill SJ

    更新日期:2010-08-01 00:00:00

  • Analysis of mice with single and multiple copies of transgenes reveals a novel arrangement for the lambda5-VpreB1 locus control region.

    abstract::The murine lambda5-VpreB1 locus encodes two proteins that form part of the pre-B-cell receptor and play a key role in B-lymphocyte development. We have identified a locus control region (LCR) which is responsible for coordinate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.671

    authors: Sabbattini P,Georgiou A,Sinclair C,Dillon N

    更新日期:1999-01-01 00:00:00

  • CENP-A reduction induces a p53-dependent cellular senescence response to protect cells from executing defective mitoses.

    abstract::Cellular senescence is an irreversible growth arrest and is presumed to be a natural barrier to tumor development. Like telomere shortening, certain defects in chromosome integrity can trigger senescence; however, the roles of centromere proteins in regulating commitment to the senescent state remains to be establishe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01318-09

    authors: Maehara K,Takahashi K,Saitoh S

    更新日期:2010-05-01 00:00:00

  • The USP1/UAF1 complex promotes double-strand break repair through homologous recombination.

    abstract::Protein ubiquitination plays a key role in the regulation of a variety of DNA repair mechanisms. Protein ubiquitination is controlled by the coordinate activity of ubiquitin ligases and deubiquitinating enzymes (DUBs). The deubiquitinating enzyme USP1 regulates DNA repair and the Fanconi anemia pathway through its ass...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05058-11

    authors: Murai J,Yang K,Dejsuphong D,Hirota K,Takeda S,D'Andrea AD

    更新日期:2011-06-01 00:00:00

  • p57(Kip2) stabilizes the MyoD protein by inhibiting cyclin E-Cdk2 kinase activity in growing myoblasts.

    abstract::We show that expression of p57(Kip2), a potent tight-binding inhibitor of several G(1) cyclin-cyclin-dependent kinase (Cdk) complexes, increases markedly during C2C12 myoblast differentiation. We examined the effect of p57(Kip2) on the activity of the transcription factor MyoD. In transient transfection assays, transc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.11.7621

    authors: Reynaud EG,Pelpel K,Guillier M,Leibovitch MP,Leibovitch SA

    更新日期:1999-11-01 00:00:00

  • A role for c-myc in chemically induced renal-cell death.

    abstract::A variety of genes, including c-myc, are activated by chemical toxicants in vivo and in vitro. Although enforced c-myc expression induces apoptosis after withdrawing survival factors, it is not clear if activation of the endogenous c-myc gene is an apoptotic signal after toxicant exposure. The renal tubular epithelium...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.11.6755

    authors: Zhan Y,Cleveland JL,Stevens JL

    更新日期:1997-11-01 00:00:00

  • Negative regulatory gene for general control of amino acid biosynthesis in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, many amino acid biosynthetic pathways are coregulated by a complex general control system: starvation for a single amino acid results in the derepression of amino acid biosynthetic genes in multiple pathways. Derepression of these genes is mediated by positive (GCN) and negative (GCD) regu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.9.3150

    authors: Myers PL,Skvirsky RC,Greenberg ML,Greer H

    更新日期:1986-09-01 00:00:00

  • Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression.

    abstract::COUP-TF, an orphan member of the nuclear receptor superfamily, has been proposed to play a key role in regulating organogenesis, neurogenesis, and cellular differentiation during embryonic development. Since heterodimierization is a common theme within the nuclear receptor superfamily and has been demonstrated to modu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.5.2332

    authors: Leng X,Cooney AJ,Tsai SY,Tsai MJ

    更新日期:1996-05-01 00:00:00

  • Phenotypic characterization of the murine Nkx2.6 homeobox gene by gene targeting.

    abstract::The NK-2 homeobox genes have been shown to play critical roles in the development of specific organs and tissues. Nkx2.6 is a member of the NK-2 homeobox gene family and is most closely related to the Drosophila tinman gene. Nkx2.6 is expressed in the caudal pharyngeal pouches, the caudal heart progenitors, the sinus ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.8.2874-2879.2000

    authors: Tanaka M,Yamasaki N,Izumo S

    更新日期:2000-04-01 00:00:00

  • Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha.

    abstract::The molecular chaperone HSP90 regulates stability and function of multiple protein kinases. The HSP90-binding drug geldanamycin interferes with this activity and promotes proteasome-dependent degradation of most HSP90 client proteins. Geldanamycin also binds to GRP94, the HSP90 paralog located in the endoplasmic retic...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.24.8506-8513.2002

    authors: Marcu MG,Doyle M,Bertolotti A,Ron D,Hendershot L,Neckers L

    更新日期:2002-12-01 00:00:00

  • Six4, a putative myogenin gene regulator, is not essential for mouse embryonal development.

    abstract::Six4 is a member of the Six family genes, homologues of Drosophila melanogaster sine oculis. The gene is thought to be involved in neurogenesis, myogenesis, and development of other organs, based on its specific expression in certain neuronal cells of the developing embryo and in adult skeletal muscles. To elucidate t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.10.3343-3350.2001

    authors: Ozaki H,Watanabe Y,Takahashi K,Kitamura K,Tanaka A,Urase K,Momoi T,Sudo K,Sakagami J,Asano M,Iwakura Y,Kawakami K

    更新日期:2001-05-01 00:00:00

  • The Caenorhabditis elegans EGL-15 signaling pathway implicates a DOS-like multisubstrate adaptor protein in fibroblast growth factor signal transduction.

    abstract::EGL-15 is a fibroblast growth factor receptor in the nematode Caenorhabditis elegans. Components that mediate EGL-15 signaling have been identified via mutations that confer a Clear (Clr) phenotype, indicative of hyperactivity of this pathway, or a suppressor-of-Clr (Soc) phenotype, indicative of reduced pathway activ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.23.8104-8116.2001

    authors: Schutzman JL,Borland CZ,Newman JC,Robinson MK,Kokel M,Stern MJ

    更新日期:2001-12-01 00:00:00

  • Glycosylation and secretion of human tissue plasminogen activator in recombinant baculovirus-infected insect cells.

    abstract::Cell lines established from the lepidopteran insect Spodoptera frugiperda (fall armyworm; Sf9) are used routinely as hosts for the expression of foreign proteins by recombinant baculovirus vectors. We have examined the pathway of protein glycosylation and secretion in these cells, using human tissue plasminogen activa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.1.214

    authors: Jarvis DL,Summers MD

    更新日期:1989-01-01 00:00:00