title: 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.
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Abhilash K
authors: AK
authors: Ravindranath
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Swayamjot
authors: S
authors: Kaur
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Roman P
authors: RP
authors: Wernyj
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Muthu N
authors: MN
authors: Kumaran
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|Present address: Delaware State University, Dover, DE, USA.
authors: Karl E
authors: KE
authors: Miletti-Gonzalez
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Rigel
authors: R
authors: Chan
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors: Elaine
authors: E
authors: Lim
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
authors: Kiran
authors: K
authors: Madura
authors: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|Department of Obstetrics and Gynecology, New Brunswick, Rutgers Cancer Institute of New Jersey, NJ, USA.
authors: Lorna
authors: L
authors: Rodriguez-Rodriguez
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D041702:BALB 3T3 Cells; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D034622:RNA Interference; D012694:Serine; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; C497483:CD44 protein, human; D044783:F-Box Proteins; C000607216:FBXO21 protein, human; D018960:Hyaluronan Receptors; D012694:Serine; D046988:Proteasome Endopeptidase Complex
keywords: drug resistance; ubquitination