Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein

Keiichiro Okuhira, Nobumichi Ohoka, Kimie Sai, Tomoko Nishimaki-Mogami, Yukihiro Itoh, Minoru Ishikawa, Yuichi Hashimoto, Mikihiko Naito

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

Manipulation of protein stability with small molecules is a challenge in the field of drug discovery. Here we show that cellular retinoic acid binding protein-II (CRABP-II) can be specifically degraded by a novel compound, SNIPER-4, consisting of (-)-N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butyryl]-l- leucine methyl ester and all-trans retinoic acid that are ligands for cellular inhibitor of apoptosis protein 1 (cIAP1) and CRABP-II, respectively. Mechanistic analysis revealed that SNIPER-4 induces cIAP1-mediated ubiquitylation of CRABP-II, resulting in the proteasomal degradation. The protein knockdown strategy employing the structure of SNIPER-4 could be applicable to other target proteins.

Original languageEnglish
Pages (from-to)1147-1152
Number of pages6
JournalFEBS Letters
Volume585
Issue number8
DOIs
Publication statusPublished - 2011 Apr 20
Externally publishedYes

Keywords

  • Cellular inhibitor of apoptosis protein 1
  • Cellular retinoic acid binding protein-II
  • Proteasome
  • Protein knockdown
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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