Skp2 inhibitors: Novel anticancer strategies

Yeongju Lee, Hyun-Suk Lim

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Skp2 is frequently overexpressed in many human cancers and plays a key role in tumorigenesis. As a component of the SCFSkp2 ubiquitin E3 ligase complex, Skp2 is responsible for recruiting substrate proteins for their ubiquitination and subsequent degradation by the 26S proteasome. Thus, Skp2 promotes the cell cycle by down-regulating cell cycle proteins such as the tumor suppressor p27. Alternatively, Skp2 suppresses p53-dependent apoptosis by outcompeting p53 for binding to p300, thereby perturbing p300-mediated p53 acetylation and stabilization. Taken together, inhibition of Skp2 functions (either proteolytic function or non-proteolytic function) is emerging as a promising and novel anti-cancer strategy. In the present review, we highlight the development of Skp2 inhibitors with different mechanisms of action.

Original languageEnglish (US)
Pages (from-to)2363-2379
Number of pages17
JournalCurrent Medicinal Chemistry
Volume23
Issue number22
DOIs
StatePublished - Jul 1 2016

Fingerprint

Acetylation
Neoplasms
Cell Cycle Proteins
Ubiquitin-Protein Ligases
Ubiquitination
Tumors
Cell Cycle
Carcinogenesis
Stabilization
Cells
Apoptosis
Degradation
Substrates
Proteins
ATP dependent 26S protease

Keywords

  • 26S proteasome
  • E3 ligase complex
  • Skp2 inhibitors
  • Skp2/p27 interaction
  • Tumorigenesis
  • Ubiquitinproteasome system

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Skp2 inhibitors : Novel anticancer strategies. / Lee, Yeongju; Lim, Hyun-Suk.

In: Current Medicinal Chemistry, Vol. 23, No. 22, 01.07.2016, p. 2363-2379.

Research output: Contribution to journalReview article

Lee, Yeongju ; Lim, Hyun-Suk. / Skp2 inhibitors : Novel anticancer strategies. In: Current Medicinal Chemistry. 2016 ; Vol. 23, No. 22. pp. 2363-2379.
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