Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression

Boglárka Zámbó, Zsuzsa Bartos, Orsolya Mózner, Edit Szabó, György Várady, G. Poór, Márton Pálinkás, H. Andrikovics, T. Hegedűs, L. Homolya, B. Sarkadi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins.

Original languageEnglish
Article number7487
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Erythrocyte Membrane
Membrane Proteins
Gout
Mutation
Precision Medicine
Proteins
Genetic Testing
Multiple Drug Resistance
Xenobiotics
Mutant Proteins
Molecular Dynamics Simulation
Uric Acid
Healthy Volunteers
Pharmacology
ATP Binding Cassette Transporter, Sub-Family G, Member 2
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression. / Zámbó, Boglárka; Bartos, Zsuzsa; Mózner, Orsolya; Szabó, Edit; Várady, György; Poór, G.; Pálinkás, Márton; Andrikovics, H.; Hegedűs, T.; Homolya, L.; Sarkadi, B.

In: Scientific Reports, Vol. 8, No. 1, 7487, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Várady, György

AU - Poór, G.

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