Cmdr1, a Chicken P-Glycoprotein, Confers Multidrug Resistance and Interacts with Estradiol
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H.M.L. Edelmann
Abstract
We have cloned from a chicken intestinal cDNA library Cmdr1, the first avian P-glycoprotein. Cmdr1 is 67% and 69% identical to proteins encoded by the human MDR1 and MDR2 genes, respectively. Functional expression of Cmdr1 in both mouse NIH 3T3 and yeast cells demonstrated that Cmdr1 represents the avian ortholog of human Mdr1, since it confers resistance to several anticancer drugs and the fluorescent dye rhodamine 6G. Northern and immunoblot analysis showed that CMDR1 is highly expressed throughout the intestine and in the liver, and to a considerable extent in kidney, brain, lung, heart, eye and follicles. In situ hybridization revealed a cell type-specific expression of CMDR1 in the intestinal epithelium, with high levels in the villi of the small and large intestine as well as crypt cells. These data suggest that Cmdr1 could play a role in intestinal detoxification. Most interestingly, immunoblotting showed that Cmdr1 is also expressed in ovarian tissues, particularly in theca cells, the major site for ovarian estrogen production in birds. Indeed, competition experiments indicated that Cmdr1 interacts with estradiol, since rhodamine 6G efflux was efficiently blocked by estradiol in NIH 3T3 cells expressing Cmdr1. Rhodamine efflux was also blocked by PSC-833, a specific inhibitor of steroid-transporting P-glycoproteins from mammalian cells. We propose that Cmdr1 in ovarian cells could be involved in the cell type-specific transport or release of estrogen that is essential for avian follicular development.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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Artikel in diesem Heft
- Editors Note
- Shoulder Hopping on Giants
- Moving from Zurich to Vienna Up or Down?
- The IMP and European Molecular Biology: Moving the Centre Eastwards
- Max, the Vienna Biocenter and Other Spin Off
- The Functions of Breast Cancer Susceptibility Gene 1 (BRCA1) Product and Its Associated Proteins
- Lymphocyte Antigen Receptor Signal Integration and Regulation by the SHC Adaptor
- New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle
- Being at the Right Place at the Right Time: The Role of Nuclear Transport in Dynamic Transcriptional Regulation in Yeast
- Plectin: A Cytolinker by Design
- Regulation of the Sea Urchin Early H2A Histone Gene Expression Depends on the Modulator Element and on Sequences Located near the 3′ End
- A Ribosomal Orphon Sequence from <I>Xenopus laevis</I> Flanked by Novel Low Copy Number Repetitive Elements
- Characterization of the Transcription Factor MTF-1 from the Japanese Pufferfish (<I>Fugu rubripes</I>) Reveals Evolutionary Conservation of Heavy Metal Stress Response
- A Novel Way to Induce Erythroid Progenitor Self Renewal: Cooperation of c-Kit with the Erythropoietin Receptor
- An Unexpected Role for p53 in Augmenting SV40 Large T Antigen-Mediated Tumorigenesis
- The Epstein-Barr Virus Nuclear Antigen 2 (EBNA2), a Protein Required for B Lymphocyte Immortalization, Induces the Synthesis of Type I Interferon in Burkitts Lymphoma Cell Lines
- Regulation of Human c-Abl Tyrosine Kinase Activity in <I>Xenopus</I> Oocytes and Acceleration of Progesterone-Induced G2/M Transition by Oncogenic Forms
- Cmdr1, a Chicken P-Glycoprotein, Confers Multidrug Resistance and Interacts with Estradiol
- Probing Ribosome Structure by Europium-Induced RNA Cleavage
- The Oct-1 POU Domain Directs Developmentally Regulated Nuclear Translocation in Xenopus Embryos
- Constitutive Expression of Interleukin-1beta (IL-1beta) in Rat Oligodendrocytes
- Conformational Study of the HIV-1 Reverse Transcriptase Inhibitor 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
- Transient Transfection of Mammary Epithelial Cells with a PEI/DNA/Adenovirus System
