High-throughput screening AlphaScreen assay for identification of small-molecule inhibitors of ubiquitin E3 ligase SCFSkp2-Cks1.

ABSTRACT: Decreased levels of cell cycle inhibitor p27(Kip1) due to excessive degradation occur in a variety of aggressive human tumors. Since reduced p27(Kip1) expression has been associated with a poor prognosis in many human cancers and resistance to certain antitumor therapies, elevation of p27(Kip1) expression could improve prognosis and prevent excessive cell proliferation. SCF(Skp2) is one of the major ubiquitin E3 ligases responsible for degradation of p27(Kip1). Ubiquitination of p27(Kip1) also requires a small adaptor protein, Cks1, which facilitates substrate recruitment by bridging the interaction between Skp2 and p27(Kip1). It has been shown previously that a direct interaction between Cks1 and Skp2 is required for p27(Kip1) degradation. Accordingly, perturbation of the Skp2-Cks1 intera

SUBMITTER: Ungermannova D 

PROVIDER: S-EPMC4168015 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature