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CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.


ABSTRACT: 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.

SUBMITTER: Ravindranath AK 

PROVIDER: S-EPMC4694903 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.

Ravindranath Abhilash K AK   Kaur Swayamjot S   Wernyj Roman P RP   Kumaran Muthu N MN   Miletti-Gonzalez Karl E KE   Chan Rigel R   Lim Elaine E   Madura Kiran K   Rodriguez-Rodriguez Lorna L  

Oncotarget 20150901 28


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. ...[more]

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