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

doi:10.1016/j.febslet.2011.03.019

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

LIF - Molecular and Chemical Life Science

Research output: Contribution to journal › Article › peer-review

74 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 language	English
Pages (from-to)	1147-1152
Number of pages	6
Journal	FEBS Letters
Volume	585
Issue number	8
DOIs	https://doi.org/10.1016/j.febslet.2011.03.019
Publication status	Published - 2011 Apr 20

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

Access to Document

10.1016/j.febslet.2011.03.019

Fingerprint Dive into the research topics of 'Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein'. Together they form a unique fingerprint.

Cite this

Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein. / Okuhira, Keiichiro; Ohoka, Nobumichi; Sai, Kimie; Nishimaki-Mogami, Tomoko; Itoh, Yukihiro; Ishikawa, Minoru; Hashimoto, Yuichi; Naito, Mikihiko.

In: FEBS Letters, Vol. 585, No. 8, 20.04.2011, p. 1147-1152.

Research output: Contribution to journal › Article › peer-review

@article{73c4488f055e411a91301fa54422db8c,

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

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.",

keywords = "Cellular inhibitor of apoptosis protein 1, Cellular retinoic acid binding protein-II, Proteasome, Protein knockdown, Ubiquitin",

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

note = "Funding Information: We thank Nippon Kayaku Co. Ltd. , for kindly providing MeBS. This study was supported in part by Grants-in-Aids for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and by the research grant of Astellas Foundation for Research on Metabolic Disorders. ",

year = "2011",

month = apr,

day = "20",

doi = "10.1016/j.febslet.2011.03.019",

language = "English",

volume = "585",

pages = "1147--1152",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "8",

}

TY - JOUR

T1 - Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein

AU - Okuhira, Keiichiro

AU - Ohoka, Nobumichi

AU - Sai, Kimie

AU - Nishimaki-Mogami, Tomoko

AU - Itoh, Yukihiro

AU - Ishikawa, Minoru

AU - Hashimoto, Yuichi

AU - Naito, Mikihiko

N1 - Funding Information: We thank Nippon Kayaku Co. Ltd. , for kindly providing MeBS. This study was supported in part by Grants-in-Aids for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and by the research grant of Astellas Foundation for Research on Metabolic Disorders.

PY - 2011/4/20

Y1 - 2011/4/20

N2 - 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.

AB - 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.

KW - Cellular inhibitor of apoptosis protein 1

KW - Cellular retinoic acid binding protein-II

KW - Proteasome

KW - Protein knockdown

KW - Ubiquitin

UR - http://www.scopus.com/inward/record.url?scp=79954445413&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954445413&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2011.03.019

DO - 10.1016/j.febslet.2011.03.019

M3 - Article

C2 - 21414315

AN - SCOPUS:79954445413

VL - 585

SP - 1147

EP - 1152

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 8

ER -