pevonedistat and apcin

pevonedistat has been researched along with apcin* in 1 studies

Other Studies

1 other study(ies) available for pevonedistat and apcin

ArticleYear
Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation.
    Cancer letters, 2017, 01-28, Volume: 385

    Recent studies revealed that mutations in SPOP (Speckle-type POZ protein) occur in up to 15% of patients with prostate cancer. However, the physiological role of SPOP in regulating prostate tumorigenesis remains elusive. Here, we identified the Cdc20 oncoprotein as a novel ubiquitin substrate of SPOP. As such, pharmacological inhibition of Cullin-based E3 ligases by MLN4924 could stabilize endogenous Cdc20 in cells. Furthermore, we found that Cullin 3, and, to a less extent, Cullin 1, specifically interacted with Cdc20. Depletion of Cullin 3, but not Cullin 1, could upregulate the abudance of Cdc20 largely via prolonging Cdc20 half-life. Moreover, SPOP, the adaptor protein of Cullin 3 family E3 ligase, specifically interacted with Cdc20, and promoted the poly-ubiquitination and subsequent degradation of Cdc20 in a degron-dependent manner. Importantly, prostate cancer-derived SPOP mutants failed to interact with Cdc20 to promote its degradation. As a result, SPOP-deficient prostate cancer cells with elevated Cdc20 expression became resistant to a pharmacological Cdc20 inhibitor. Therefore, our results revealed a novel role of SPOP in tumorigenesis in part by promoting the degradation of the Cdc20 oncoprotein.

    Topics: Antineoplastic Agents; Carbamates; Cdc20 Proteins; Cullin Proteins; Cyclopentanes; Diamines; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Enzyme Inhibitors; HeLa Cells; Humans; Male; Molecular Targeted Therapy; Mutation; Nuclear Proteins; Prostatic Neoplasms; Protein Interaction Domains and Motifs; Proteolysis; Pyrimidines; Repressor Proteins; Time Factors; Transfection; Ubiquitination

2017