CD44通过保护P-糖蛋白免受FBXO21介导的泛素化作用来促进多药耐药。
CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.
作者信息
Ravindranath Abhilash K, Kaur Swayamjot, Wernyj Roman P, Kumaran Muthu N, Miletti-Gonzalez Karl E, Chan Rigel, Lim Elaine, Madura Kiran, Rodriguez-Rodriguez Lorna
机构信息
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Present address: Delaware State University, Dover, DE, USA.
出版信息
Oncotarget. 2015 Sep 22;6(28):26308-21. doi: 10.18632/oncotarget.4763.
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.
在此我们证明，泛素E3连接酶FBXO21靶向多药耐药转运蛋白ABCB1（也称为P-糖蛋白，P-gp），使其通过蛋白酶体降解。我们还表明，多功能蛋白和干细胞标志物CD44的Ser291磷酸化形式可抑制FBXO21介导的P-gp降解。因此，CD44增强了P-gp介导的耐药性，并且是P-gp阳性细胞中的一个潜在治疗靶点。
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