The ability of several of these membrane proteins to transport a wide range of anticancer drugs out of cells and their presence in many tumors make them prime suspects in unexplained cases of drug resistance, although proof that they contribute to clinical drug resistance is. Characterization of the human multidrug resistance protein isoform. Multidrug resistance proteins mrps and implication in. Identification and bioinformatic characterization of a. The assembly of resistance genes on a single r plasmid is achieved by mechanisms provided by transposons, integrons, and. Multidrug resistant strains of mycobacterium tuberculosis seriously threaten tuberculosis tb control and prevention efforts. Multidrug resistance in bacteria is often caused by the accumulation of genes, each coding for resistance to a single drug, on r plasmids. Pdf multiple drug resistance protein mdr1, multidrug. We summarize in this paper the recently published results on multidrug resistance associated proteins 3, 4, and 5 mrps 35.
Examples of very and moderate potent compounds in the bile salt export protein bsep vesicle assay a compounds that produce ic 50 resistance protein mdr1, multidrug resistance related protein mrp. Multidrug resistance associated proteins in multidrug. Today this fascinating protein, which is proposed to operate as an atppowered drug efflux. Function, evolution and structure of multidrug resistance protein mrp. Pglycoprotein pgp, multidrug resistance protein 1 mrp1, and breast cancer resistance protein bcrp, for example, have each been cloned from a drug resistant cancer line and are thought to mediate drug ef. The human multidrug resistance associated protein mrp family currently has seven members. The small multidrug resistance smr protein family is a bacterial multidrug transporter family. The multidrug resistance protein mrp1 is an atp binding cassette abc. Yb1 protein and multidrug resistance of tumor cells article pdf available in current signal transduction therapy 73. Evaluating the role of multidrug resistance protein 3. Function, evolution and structure of multidrug resistance protein ncbi.
These are the classical pglycoprotein mdr1, abcb1, the multidrug resistance associated proteins mrps, in the abcc subfamily, and the abcg2 protein, an. The membrane proteins mediating the adenosine triphos phate atpdependent transport of anionic conjugates and amphiphilic anions, such as the bilirubin. Structural basis of substrate recognition by the multidrug. The one shown here, sav1866 from pdb entry 2onj, is found in staphylococcus bacteria. Threedimensional reconstruction of the saccharomyces cerevisiae multidrug resistance protein pdr5p. For example, mrp2 clears certain drugs from organs and tissues, playing a part in drug metabolism. Natural products modulate the multifactorial multidrug. Permeability glycoprotein pgp and multidrug resistance protein mrp are two efflux proteins that are key participants in drug efflux at the cellular level, causing a reduced intracellular drug concentration. Multidrug resistance gentaur your supplier of research. Equally, if not more importantly, many of these drugtransporting abc proteins also mediate the cellular efflux of a broad range of physiological.
The human multidrug resistance protein mrp family contains at least six members. Examples of very and moderate potent compounds in the bile salt export protein bsep vesicle assay a compounds that produce ic 50 resistance transporters find drugs that try to gain entry through a cell membrane and they transport them back outside. The role of tmd0 in the multidrug resistance proteins, however. Overview of multidrugresistant pseudomonas aeruginosa. Pdf the role of abc transporters in drug resistance. Multidrug resistanceassociated protein1 mrp1 protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease copd. Neoplastic resistance cancer cells also have the ability to become resistant to multiple different drugs, and share many of the same mechanisms. Evaluating the role of multidrug resistance protein 3 mdr3 inhibition in predicting drug induced. Mammalian multidrugresistance proteins mrps essays in. These abc transporters together form the largest branch of proteins within the human body. The description of the multiple drug resistance protein mdr1, also called pglycoprotein, seemed to be promising for the understanding of the mechanisms of antineoplastic treatment failure. A multidrug resistant chinese hamster ovary cell line cr1r12 was obtained which constitutively expresses pglycoprotein, up to 32% by weight of plasma membrane protein. Pglycoprotein 1 permeability glycoprotein, abbreviated as pgp or pgp also known as multidrug resistance protein 1 mdr1 or atpbinding cassette subfamily b member 1 abcb1 or cluster of differentiation 243 cd243 is an important protein of the cell membrane that pumps many foreign substances out of cells.
The abcc2 gene provides instructions for producing a protein called multidrug resistance protein 2 mrp2. Multidrug resistance proteins mrps are members of the c family of a group of proteins named atpbinding cassette abc transporters. Overexpression of pgp was linked to multidrug resistance mdr in mammalian cell lines and human cancers, evoking intense interest first from molecular and cell biologists, and later, when purified pgp became available, from biochemists and biophysicists. Herein, a facile strategy is reported to construct a versatile dna nanostructure as a co. Understanding multidrug resistance multidrug resistant organisms mdros are a group of bacteria with important resistance patterns sometimes just one key drug will define a mdro methicillin resistance in staphylococcus aureus vancomycin resistance in enterococcus sp. This protein is one of a family of multidrug resistance proteins involved in the transport of substances out of cells. The human multidrug resistance protein mrp family contains at least six. Multidrug resistance transporters find drugs that try to gain entry through a cell membrane and they transport them back outside. The human multidrug resistanceassociated protein mrp family currently has seven members.
Associated protein mrpabcc proteins mylene honorat. Atpbinding cassette subfamily c member 4 abcc4, also known as the multidrug resistanceassociated protein 4 mrp4 or multispecific organic anion transporter b moatb, is a protein that in humans is encoded by the abcc4 gene. Characterization and phylogenetic analysis of multidrug. Multidrug resistance protein attenuates gemtuzumab. In the present study, atp binding cassette abc efflux transporters including breast cancer resistance protein bcrp, pglycoprotein pgpmdr1, multidrug resistance protein mrp 2, mrp3 and.
Multidrug resistance proteins wiley online library. The multidrug resistance protein family sciencedirect. No high resolution xray crystal structure is available for pgp. Original article role and mechanism of trps1 gene in.
Glutathione and multidrug resistance protein transporter. Multidrug resistanceassociated protein 2 wikipedia. Bacterial antibiotic efflux pumps are key players in antibiotic resistance. This study aimed to analyze the multidrug resistance protein mrp gene in. Molecular studies of the mechanism of action of antitubercular drugs have elucidated the genetic basis of drug resistance in m. The overexpression of multidrug resistance associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells xi chen, mu zhang and lianxin liu general surgery, the first affiliated hospital of harbin medical university, harbin, p. The atpbinding cassette abc transporters are members of a protein superfamily that are known to translocate various substrates across. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. Multidrug resistanceassociated protein1 mrp1 genetic. Multidrug resistance associated proteins in multidrug resistance. The bacterial lmra protein and the mammalian multidrug resistance pglycoprotein are closely related atpbinding cassette abc transporters that confer multidrug resistance on cells by mediating. Multiple drug resistance mdr, multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories.
Subcellular localization and activity of multidrug. The protein is composed of two identical subunits with a tunnel in between. In this study, we compared the rela tionship of trps1 expression and the expression of the multidrug resistance gene multi drug resistance 1 mdr1 in different osteosar coma cell lines as well as in human osteosarcoma tissues, and. Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Pdf yb1 protein and multidrug resistance of tumor cells. Multidrug resistance transporter1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology lynae m. Multidrug resistance associated protein 2 mrp2 also called canalicular multispecific organic anion transporter 1 cmoat or atpbinding cassette subfamily c member 2 abcc2 is a protein that in humans is encoded by the abcc2 gene. Small multidrug resistance protein also known as drug metabolite transporter is a family of integral membrane proteins that confer drug resistance to a wide range of toxic compounds by removing them for the cells. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Multidrug resistance an overview sciencedirect topics. Resistance to at least the two major antituberculosis drugs, isoniazid and rifampicin has been termed multidrugresistant tuberculosis mdrtb.
Multidrug resistance protein journal of biological chemistry. Multifactorial multidrug resistance cancer cells can not only develop resistance to one drug, but also to entire classes of drugs with similar mechanisms of action. The assembly of resistance genes on a single r plasmid is achieved by mechanisms provided by transposons, integrons, and iscr elements. In addition, the cells that comprise the bloodbrain and bloodcerebrospinal fluid barriers express multiple atpdependent, membranebound, efflux transporters, such as members of the multidrug resistance associated protein mrp family, which contribute to lowered drug accumulation. As suggested by their title, smr proteins are composed of four transmembrane. Treatment of mdrtb requires prolonged and expensive chemotherapy using secondline drugs of heightened toxicity. Thus, counteracting drug resistance is crucial to providing the best treatment. Expression of genes for the multiple drug resistance protein mdr1, multidrug resistance related protein mrp. Glutathione and multidrug resistance protein transporter mediate a selfpropelled disposal of bismuth in human cells yifan honga,b, yautsz laia, godfrey chifung chanb, and hongzhe suna,1 adepartment of chemistry and bdepartment of paediatrics and adolescent medicine, the university of hong kong, hong kong sar, peoples republic of china edited by john h. Mrp3 can transport organic compounds conjugated to glutathione, sulfate, or glucuronate, such as estradiol17. Emergence of a potent multidrug efflux pump variant that.
The ability of several of these membrane proteins to. Multidrug resistance proteins mrps and cancer therapy. Multidrug resistance transporter1 and breast cancer. Mrp1, the godfather of the family and well known as the multidrug resistance protein, and five homologs, called mrp2 6. Abc proteins play key roles in cellular detoxification of xeno and endobiotics. The overexpression of multidrug resistanceassociated. Overexpression of certain abc proteins, among them the multidrug resistance protein mdr and the multidrug resistance associated proteins mrps, contribute to drug resistance in a variety organisms ranging from parasitic protozoa to human neoplastic cells.
Increased efflux of drug as by pglycoprotein, multidrug resistance associated protein, lung resistance related protein, and breast cancer resistance protein 2. Here, we describe the emergence of a resistance enhancing variant named recmeabc of the predominant efflux pump. Mrp1, the godfather of the family and well known as the multidrug resistance protein, and five homologs, called mrp2. Original article multidrug resistance proteins in renal. The closely related multidrug efflux pumps qaca and qacb, from the bacterial pathogen staphylococcus aureus, both confer resistance to various toxic organic cations but differ in that qacb mediates lower levels of resistance to divalent cations. Multidrug resistance mdr is a major obstacle in the clinical treatment of cancer.
241 1295 145 35 1419 1495 306 428 551 1048 606 688 964 1510 858 1102 609 653 479 292 1506 1589 1431 1503 1395 705 1306 1280 55 71 30 135 872 1135 1183 791 89 1343