E3 ubiquitin ligase Skp2 as an attractive target in cancer therapy

Zhonglin Hao, Shuang Huang

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations

Abstract

E3 ubiquitin ligase Skp2 attaches ubiquitin to its target proteins and marks them for destruction by the 26S proteasome. This mechanism participates in a number of important cellular processes such as cell proliferation, DNA replication, V(D)J recombination, gene transcription, cellular metabolism and senescence. Skp2 is oncogenic. It is overexpressed in various solid tumors and hematological malignancies. Due to the antagonistic role Skp2 plays against p27, Skp2 overexpression is frequently associated with down-regulation of p27. Importantly, Skp2 overexpression in cancer cells is prognostic of cancer progression and overall survival. Recent studies have shown that Skp2 suppression might be an excellent strategy to inhibit tumorigenesis in tumors in which tumor suppressor genes such as VHL, RB or TP53 are mutated. In this review, we also summarize early efforts in the development of Skp2 inhibitors. The implications of continued, long-term Skp2 suppression are discussed.

Original languageEnglish (US)
Pages (from-to)474-490
Number of pages17
JournalFrontiers in Bioscience - Landmark
Volume20
Issue number3
DOIs
StatePublished - Jan 15 2015

Keywords

  • Cancer therapy
  • E3 ubiquitin ligase
  • Inhibitor
  • Oncogenesis
  • Review
  • Skp2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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