title: Development of a peptide-based inducer of nuclear receptors degradation.
abstract: A peptide-based protein knockdown system for inducing nuclear receptors degradation via the ubiquitin-proteasome system was developed. Specifically, the designed molecules were composed of two biologically active scaffolds: a peptide that binds to the estrogen receptor α (ERα) surface and an MV1 molecule that binds to cellular inhibitors of apoptosis proteins (IAP: cIAP1/cIAP2/XIAP) to induce ubiquitylation of the ERα. The hybrid peptides induced IAP-mediated ubiquitylation followed by proteasomal degradation of the ERα. Those peptides were also applicable for inducing androgen receptor (AR) degradation.
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: demizu@nihs.go.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Ohoka
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Nagakubo
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Institute of Biomedical Sciences, Tokushima University Graduate School, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Okuhira
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.affiliation: National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: masaaki@nihs.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
mesh_terms: D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D010455:Peptides
keywords: Helical peptide; Nuclear receptors; Protein knockdown; Protein–protein interaction