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Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules
Abstract
Multidrug resistance protein (MRP) 4 is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, which are capable of pumping a wide variety of endogenous and xenobiotic organic anionic compounds out of the cell. In addition to its role in the body distribution and renal excretion of a wide variety of antiviral, cytostatic, antibiotic and cardiovascular drugs, MRP4/ABCC4 has the remarkable ability to transport molecules involved in cellular signalling. These molecules include cyclic nucleotides, eicosanoids, urate and conjugated steroids. The unique structure, regulation and dual localisation of MRP4 in polarised cells could be connected with a key function in cellular protection and extracellular signalling pathways. This review focuses on recent insights into the versatile transport function of MRP4 and its potential as a new therapeutic target to modulate various pathophysiological signalling processes.
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ABCC4 protein is highly conserved between humans and mice, with 100% sequence identity.
“Notably, ABCC4 protein is highly conserved between humans and mice, with 100% sequence identity, suggesting functional conservation across species39,41,42.”
From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [42]
ABCC4 is localized to the basolateral membrane of hepatocytes, where it transports conjugated substrates into the bloodstream.
“Subcellularly, ABCC4 is localized to the basolateral membrane of hepatocytes, also referred to as the sinusoidal surface, where it transports several conjugated substrates into the bloodstream40–42.”
From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [42]
ABCC4 is a hepatic efflux transporter of cAMP.
“Functioning as a hepatic efflux transporter of cyclic AMP (cAMP), ABCC4 deficiency led to intracellular accumulation of cAMP, thereby activating the downstream sensor Epac2.”
From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [42]
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Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases
Chen, Z., & Tiwari, A. K. (2011) · The FEBS Journal · doi:10.1111/j.1742-4658.2011.08235.x · Cited by 274
Dysfunction of ABC transporters at the blood-brain barrier: Role in neurological disorders
Gil-Martins, E., Barbosa, D. J., Silva, V., Remião, F., & Silva, R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107554 · Cited by 152
Boyer, J. L. (2013) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2013.tb00519.x · Cited by 124
Chen, J., Huang, H., Chen, C., Xia, G., Huang, H., Xiong, Y., Luo, P., Chen, Y., Li, J., Wen, L., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08818-x · Cited by 1
Metadata
- Authors
- RUSSEL, F., KOENDERINK, J., & MASEREEUW, R.
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 29
- Issue
- 4
- Pages
- 200-207
- ISSN
- 0165-6147
- Cited by
- 383
- References
- 0
- Language
- en
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