Document Detail


pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells.
MedLine Citation:
PMID:  10438534     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several members of the ABC family of proteins have been implicated in multidrug resistance associated with cancer therapies. A novel member of this gene family, designated pABC11, has been identified using degenerate polymerase chain reaction. The full-length cDNA spans 5881 base pairs and encodes an open reading frame of 1437 amino acids predicted to contain two sets of transmembrane domains and two nucleotide binding domains characteristic of ABC proteins. The nucleotide sequence described herein extends that of three recently reported sequences, MRP5 (Kool, M., de Haas, M., Scheffer, G., Scheper, R., van Eijk, M., Juijn, J., Baas, F., and Borst, P. (1997) Cancer Res. 57, 3537-3547), SMRP (Suzuki, T., Nishio, K., Sasaki, H., Kurokawa, H., Saito-Ohara, F., Ikeuchi, T., Tanabe, S., Terada, M., and Saijo, N. (1997) Biochem. Biophys. Res. Commun. 238, 790-794), and MOAT-C (Belinsky, M., Bain, L., Balsara, B., Testa, J., and Kruh, G. (1998) J. Natl. Cancer Inst. 90, 1735-1741), in the 5' direction. Northern blot analysis detected five transcripts that were differentially expressed in several tissue types, and the gene encoding pABC11 was mapped to chromosome 3. Confocal imaging of HEK293 cells expressing a green fluorescent protein-pABC11 construct confirmed plasma membrane localization of the fusion protein. Overexpression of pABC11 resulted in reduced labeling with the fluorochromes 5-chloromethylfluorescein diacetate, fluorescein diacetate, and 2',7'-bis-(2-carboxyethyl)-5 (and-6)-carboxyfluorescein acetoxymethyl ester but not with calcein or rhodamine derivatives, consistent with pABC11 being an anion transporter. Fluorochrome export was ATP-dependent but glutathione-independent. We also show that this export pump does not confer resistance to various classes of cytotoxic drugs but does provide small but significant resistance to CdCl(2) and potassium antimonyl tartrate.
Authors:
M A McAleer; M A Breen; N L White; N Matthews
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-09-01     Completed Date:  1999-09-01     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  23541-8     Citation Subset:  IM    
Affiliation:
Yamanouchi Research Institute, Littlemore Park, Armstrong Road, Oxford OX4 4SX, United Kingdom.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF146074
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Blotting, Northern
Cell Line
Chromosome Mapping
Chromosomes, Human, Pair 3
Cloning, Molecular
Drug Resistance, Multiple / genetics*
Fluorescent Dyes / metabolism
Humans
Kidney / embryology,  metabolism*
Metals, Heavy / pharmacology
Molecular Sequence Data
Multidrug Resistance-Associated Proteins*
RNA, Messenger / genetics,  metabolism
Recombinant Fusion Proteins / metabolism
Subcellular Fractions / metabolism
Chemical
Reg. No./Substance:
0/ABCC5 protein, human; 0/ATP-Binding Cassette Transporters; 0/Fluorescent Dyes; 0/Metals, Heavy; 0/Multidrug Resistance-Associated Proteins; 0/RNA, Messenger; 0/Recombinant Fusion Proteins

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