NEDD8 Inhibition Overcomes CKS1B-Induced Drug Resistance by Upregulation of p21 in Multiple Myeloma.

ABSTRACT:

Purpose

CKS1B is significantly upregulated in multiple myeloma and associated with poor prognosis. The identification of novel therapies is essential for effective treatment of patients resistant to chemotherapy. The NEDD8 inhibitor MLN4924 selectively targets SCF(Skp2) activation and offers a more specific approach to protein degradation inhibition than total proteasomal inhibition. The goal of this study was to evaluate whether MLN4924 is effective in high CKS1B conditions and identify mechanisms regulating drug potency.

Experimental design

Bortezomib and MLN4924 sensitivity was assessed through proliferation, viability, clonogenic potential, and senescence induction in cells overexpressing CKS1B. The mechanism for MLN4924 sensitivity was elucidated by immunoblot analysis

SUBMITTER: Huang J 

PROVIDER: S-EPMC4804624 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature