蛋白敲除技术：泛素连接酶在癌症治疗中的应用

Title:Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy

Volume: 16 Issue: 2

Author(s): Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori and Mikihiko Naito

Affiliation:

关键词: IAP，PROTAC（蛋白靶向嵌合分子），蛋白酶体，蛋白敲除，SNIPER（特异性和非遗传性的IAP依赖蛋白消除），泛素连接酶。

摘要: Selective degradation of pathogenic proteins by small molecules in cells is a novel approach for development of therapeutic agents against various diseases, including cancer. We and others have developed a protein knockdown technology with a series of hybrid small compounds, called SNIPERs (Specific and Nongenetic IAP-dependent Protein ERasers); and peptidic chimeric molecules, called PROTACs (proteolysis-targeting chimeric molecules), which induce selective degradation of target proteins via the ubiquitin-proteasome pathway. These compounds include two different ligands connected by a linker; one is a ligand for a ubiquitin ligase and the other is a ligand for the target protein, which are expected to crosslink these proteins in cells. Theoretically, any cytosolic protein can be targeted for degradation by this technology. To date, several SNIPERs and PROTACs against various oncogenic proteins have been developed, which specifically induce polyubiquitylation and proteasomal degradation of the oncogenic proteins, resulting in cell death, growth arrest, or impaired migration of cancer cells. Thus, this protein knockdown technology has a great potential for cancer therapy.

Cite this article as:

Nobumichi Ohoka, Norihito Shibata, Takayuki Hattori and Mikihiko Naito , Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009616666151112122502