TY - JOUR
T1 - CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination
AU - Ravindranath, Abhilash K.
AU - Kaur, Swayamjot
AU - Wernyj, Roman P.
AU - Kumaran, Muthu N.
AU - Miletti-Gonzalez, Karl E.
AU - Chan, Rigel
AU - Lim, Elaine
AU - Madura, Kiran
AU - Rodriguez-Rodriguez, Lorna
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Dug resistance
KW - Ubquitination
UR - http://www.scopus.com/inward/record.url?scp=84944463278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944463278&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4763
DO - 10.18632/oncotarget.4763
M3 - Article
C2 - 26299618
AN - SCOPUS:84944463278
SN - 1949-2553
VL - 6
SP - 26308
EP - 26321
JO - Oncotarget
JF - Oncotarget
IS - 28
ER -