RSK1 protects P-glycoprotein/ABCB1 against ubiquitin–proteasomal degradation by downregulating the ubiquitin-conjugating enzyme E2 R1

摘要: P-glycoprotein (P-gp) is a critical determinant of multidrug resistance in cancer. We previously reported that MAPK inhibition downregulates P-gp expression and undergoes ubiquitin–proteasomal degradation regulated by UBE2R1 SCFFbx15. Here, we investigated the crosstalk between P-gp. Proteasome inhibitors or knockdown FBXO15 and/or cancelled MEK inhibitor-induced downregulation. RSK1 phosphorylated Thr162 on but did not phosphorylate FBXO15. RSK increased UBE2R1-WT UBE2R1-T162D -T162A expression. showed higher self-ubiquitination destabilisation than -T162A. Unlike -T162A, induce ubiquitination. downregulated upregulated rhodamine 123 level sensitivity to vincristine doxorubicin. However, confer any change expression, accumulation drugs. These results suggest protects against ubiquitination reducing stability.