Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism

The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and incre...

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Autores principales: Mózner, Orsolya, Bartos, Zsuzsa, Zámbó, Boglárka, Homolya, László, Hegedűs, Tamás, Sarkadi, Balázs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830335/
https://www.ncbi.nlm.nih.gov/pubmed/31597297
http://dx.doi.org/10.3390/cells8101215
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author Mózner, Orsolya
Bartos, Zsuzsa
Zámbó, Boglárka
Homolya, László
Hegedűs, Tamás
Sarkadi, Balázs
author_facet Mózner, Orsolya
Bartos, Zsuzsa
Zámbó, Boglárka
Homolya, László
Hegedűs, Tamás
Sarkadi, Balázs
author_sort Mózner, Orsolya
collection PubMed
description The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and increased drug toxicity. In this paper, we overview the key cellular pathways involved in the processing and trafficking of large membrane proteins, focusing on ABC transporters. We discuss the information available for disease-causing polymorphic variants and selected mutations of ABCG2, causing increased degradation and impaired travelling of the transporter to the plasma membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized loop region of the ABCG2 protein, in which a recently discovered mutation may actually promote ABCG2 membrane expression. We suggest that post-translational modifications in this unstructured loop at the cytoplasmic surface of the protein may have special influence on ABCG2 processing and trafficking.
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spelling pubmed-68303352019-11-20 Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism Mózner, Orsolya Bartos, Zsuzsa Zámbó, Boglárka Homolya, László Hegedűs, Tamás Sarkadi, Balázs Cells Review The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and increased drug toxicity. In this paper, we overview the key cellular pathways involved in the processing and trafficking of large membrane proteins, focusing on ABC transporters. We discuss the information available for disease-causing polymorphic variants and selected mutations of ABCG2, causing increased degradation and impaired travelling of the transporter to the plasma membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized loop region of the ABCG2 protein, in which a recently discovered mutation may actually promote ABCG2 membrane expression. We suggest that post-translational modifications in this unstructured loop at the cytoplasmic surface of the protein may have special influence on ABCG2 processing and trafficking. MDPI 2019-10-08 /pmc/articles/PMC6830335/ /pubmed/31597297 http://dx.doi.org/10.3390/cells8101215 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mózner, Orsolya
Bartos, Zsuzsa
Zámbó, Boglárka
Homolya, László
Hegedűs, Tamás
Sarkadi, Balázs
Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title_full Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title_fullStr Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title_full_unstemmed Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title_short Cellular Processing of the ABCG2 Transporter—Potential Effects on Gout and Drug Metabolism
title_sort cellular processing of the abcg2 transporter—potential effects on gout and drug metabolism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830335/
https://www.ncbi.nlm.nih.gov/pubmed/31597297
http://dx.doi.org/10.3390/cells8101215
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