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Specific degradation of CRABP‐II via cIAP1‐mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein
Author(s) -
Okuhira Keiichiro,
Ohoka Nobumichi,
Sai Kimie,
Nishimaki-Mogami Tomoko,
Itoh Yukihiro,
Ishikawa Minoru,
Hashimoto Yuichi,
Naito Mikihiko
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.03.019
Subject(s) - ubiquitin , degradation (telecommunications) , chemistry , microbiology and biotechnology , biophysics , biochemistry , biology , gene , computer science , telecommunications
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 ‐[(2 S ,3 R )‐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.