CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.
Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation. We also show that the Ser291-phosphorylated form of the multifunctional protein and stem cell marker, CD44, inhibits FBXO21-directed degradation of P-gp. Thus, CD44 increases P-gp mediated drug resistance ... and represents a potential therapeutic target in P-gp-positive cells.
Mesh Terms:
ATP Binding Cassette Transporter, Subfamily B, Animals, BALB 3T3 Cells, Drug Resistance, Multiple, Drug Resistance, Neoplasm, F-Box Proteins, Female, Humans, Hyaluronan Receptors, MCF-7 Cells, Mice, Phosphorylation, Proteasome Endopeptidase Complex, Protein Binding, Protein Stability, Proteolysis, RNA Interference, Serine, Time Factors, Transfection, Two-Hybrid System Techniques, Ubiquitination
ATP Binding Cassette Transporter, Subfamily B, Animals, BALB 3T3 Cells, Drug Resistance, Multiple, Drug Resistance, Neoplasm, F-Box Proteins, Female, Humans, Hyaluronan Receptors, MCF-7 Cells, Mice, Phosphorylation, Proteasome Endopeptidase Complex, Protein Binding, Protein Stability, Proteolysis, RNA Interference, Serine, Time Factors, Transfection, Two-Hybrid System Techniques, Ubiquitination
Oncotarget
Date: Sep. 22, 2015
PubMed ID: 26299618
View in: Pubmed Google Scholar
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