Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells.

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Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B

Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells.

Biochem Biophys Res Commun. 2001 Jul 6;285(1):111-7.

PubMed ID

11437380 [ View in PubMed

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Abstract

ABCG2 (also called MXR (3), BCRP (4), or ABCP (5) is a recently-identified ABC half-transporter, which causes multidrug resistance in cancer. Here we report that the expression of the ABCG2 protein in Sf9 insect cells resulted in a high-capacity, vanadate-sensitive ATPase activity in isolated membrane preparations. ABCG2 was expressed underglycosylated, and its ATPase activity was stimulated by daunorubicin, doxorubicin, mitoxantrone, prazosin and rhodamine 123, compounds known to be transported by this protein. ABCG2-ATPase was inhibited by low concentrations of Na-orthovanadate, N-ethylmaleimide and cyclosporin A. Verapamil had no effect, while Fumitremorgin C, reversing ABCG2-dependent cancer drug resistance, strongly inhibited this ATPase activity. The functional expression of ABCG2 in this heterologous system indicates that no additional partner protein is required for the activity of this multidrug transporter, probably working as a homodimer. We suggest that the Sf9 cell membrane ATPase system is an efficient tool for examining the interactions of ABCG2 with pharmacological agents.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cyclosporine	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Inhibitor	Details
Daunorubicin	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Substrate	Details
Doxorubicin	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Substrate	Details
Mitoxantrone	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Substrate	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cyclosporine	ATP-binding cassette sub-family G member 2	Ki (nM)	500	N/A	N/A	Details