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-d...

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Autores principales: Ravindranath, Abhilash K., Kaur, Swayamjot, Wernyj, Roman P., Kumaran, Muthu N., Miletti-Gonzalez, Karl E., Chan, Rigel, Lim, Elaine, Madura, Kiran, Rodriguez-Rodriguez, Lorna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694903/
https://www.ncbi.nlm.nih.gov/pubmed/26299618
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author Ravindranath, Abhilash K.
Kaur, Swayamjot
Wernyj, Roman P.
Kumaran, Muthu N.
Miletti-Gonzalez, Karl E.
Chan, Rigel
Lim, Elaine
Madura, Kiran
Rodriguez-Rodriguez, Lorna
author_facet Ravindranath, Abhilash K.
Kaur, Swayamjot
Wernyj, Roman P.
Kumaran, Muthu N.
Miletti-Gonzalez, Karl E.
Chan, Rigel
Lim, Elaine
Madura, Kiran
Rodriguez-Rodriguez, Lorna
author_sort Ravindranath, Abhilash K.
collection PubMed
description 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.
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spelling pubmed-46949032016-01-20 CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination Ravindranath, Abhilash K. Kaur, Swayamjot Wernyj, Roman P. Kumaran, Muthu N. Miletti-Gonzalez, Karl E. Chan, Rigel Lim, Elaine Madura, Kiran Rodriguez-Rodriguez, Lorna Oncotarget Research Paper 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. Impact Journals LLC 2015-07-03 /pmc/articles/PMC4694903/ /pubmed/26299618 Text en Copyright: © 2015 Ravindranath et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ravindranath, Abhilash K.
Kaur, Swayamjot
Wernyj, Roman P.
Kumaran, Muthu N.
Miletti-Gonzalez, Karl E.
Chan, Rigel
Lim, Elaine
Madura, Kiran
Rodriguez-Rodriguez, Lorna
CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title_full CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title_fullStr CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title_full_unstemmed CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title_short CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
title_sort cd44 promotes multi-drug resistance by protecting p-glycoprotein from fbxo21-mediated ubiquitination
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694903/
https://www.ncbi.nlm.nih.gov/pubmed/26299618
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