Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1

Sci Rep. 2021 Oct 26;11(1):21105. doi: 10.1038/s41598-021-00646-3.

Abstract

S-phase kinase associated protein 2 (Skp2), a member of the F-box family that constitute the largest known class of ubiquitin E3 specificity components, is responsible for recognizing and recruiting cyclin-dependent kinase inhibitor p27 for its ubiquitination in the presence of the small accessory protein cyclin-dependent kinase regulatory subunit 1(Cks1). Skp2 is overexpressed in esophageal carcinoma tissues and closely related with tumor poor prognosis, and perturbation of the Skp2-Cks1 interaction by inhibitors or RNAi could inhibit the proliferation and metastasis of tumor cells. Therefore, inhibition of Skp2 function by small-molecule compounds targeting Skp2-Cks1 interaction is emerging as a promising and novel anti-cancer strategy. In this study, we establish an improved high-throughput screening platform to screen Skp2 inhibitors targeting Skp2-Cks1interaction, which may provide a new therapeutic approach for the clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • CDC2-CDC28 Kinases* / antagonists & inhibitors
  • CDC2-CDC28 Kinases* / chemistry
  • CDC2-CDC28 Kinases* / genetics
  • Drug Screening Assays, Antitumor
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / enzymology
  • Esophageal Neoplasms* / genetics
  • Humans
  • Protein Kinase Inhibitors / chemistry*
  • S-Phase Kinase-Associated Proteins* / agonists
  • S-Phase Kinase-Associated Proteins* / chemistry
  • S-Phase Kinase-Associated Proteins* / genetics

Substances

  • Antineoplastic Agents
  • CKS1B protein, human
  • Protein Kinase Inhibitors
  • S-Phase Kinase-Associated Proteins
  • SKP2 protein, human
  • CDC2-CDC28 Kinases