SNIPER (Specific and Nongenetic IAP-mediated Protein ERaser) is a hybrid molecule composed of a ligand for cIAP1 (bestatin, BS) linked to another ligand (X) for a target protein, which is designed to cross-link cIAP1 and the target protein, thereby inducing IAP-mediated ubiquitylation and proteasomal degradation of the target protein (Fig.1).   We initially employed all-trans retinoic acid (ATRA) to target cellular retinoic acid binding protein-II (CRABP-II), and SNIPER(CRABP) reduced the CRABP-II protein in the cells within several hours. With its modular structure, SNIPER technology can be easily applied to other target proteins. By using tamoxifen as a ligand, we also developed SNIPER(ER) to target estrogen receptor-alpha (ERa) (Fig.2). The SNIPER(ER) induces degradation of ERa followed by necrotic cell death in breast cancer cells. Thus, SNIPER can target a variety of cytosolic proteins for degradation, which might be useful for biological researches and therapeutic purposes.

SNIPER: Inducing protein degradation via recruitment to IAP

248th National Meeting (2014)

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