Oncotarget

Research Papers:

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

Abhilash K. Ravindranath, Swayamjot Kaur, Roman P. Wernyj, Muthu N. Kumaran, Karl E. Miletti-Gonzalez, Rigel Chan, Elaine Lim, Kiran Madura and Lorna Rodriguez-Rodriguez _

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Oncotarget. 2015; 6:26308-26321. https://doi.org/10.18632/oncotarget.4763

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Abstract

Abhilash K. Ravindranath1, Swayamjot Kaur1, Roman P. Wernyj1, Muthu N. Kumaran1, Karl E. Miletti-Gonzalez1,4, Rigel Chan1, Elaine Lim1, Kiran Madura1,2 and Lorna Rodriguez-Rodriguez1,3

1 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

2 Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA

3 Department of Obstetrics and Gynecology, New Brunswick, Rutgers Cancer Institute of New Jersey, NJ, USA

4 Present address: Delaware State University, Dover, DE, USA

Correspondence to:

Lorna Rodriguez-Rodriguez, email:

Keywords: drug resistance, ubquitination

Received: January 16, 2015 Accepted: June 25, 2015 Published: July 03, 2015

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.


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