repository
Engineering of "E3 ubiquitin ligase recruiting ligand fused to cytosol-penetrating antibody" to degrade cytosolic β-catenin
- Author(s)
- 권혜진
- Advisor
- 김용성
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2020-08
- Language
- eng
- Alternative Abstract
- Oncogenic protein degradation approach has emerged as a new concept to overcome the limitation of classical monoclonal antibody therapy. Some researches on cytosolic protein degradation using small molecule or polypeptides has been conducted, but not complete IgG-format. Here, for the first time, I report eliminating cytosolic β-catenin using cytosol-penetrating antibody in human IgG1 format. I engineered β-catenin specific antibody (inBC) with improved anti-tumor activity by fusion with E3 ubiquitin ligase, termed inBC-E3. I found that inBC-VHL recruits Cul2 E3 complex in the proximity of the neo-substrate β-catenin, thus entering to ubiquitin proteasome pathway for degradation. inBC-VHL exhibits tumor growth inhibition in vitro and in vivo according to β-catenin depletion by conferring β-catenin degradation activity to inBC, which had no tumor suppressive effect. My results identified that engagement of ubiquitination cascade to the cancer-related protein for degradation offers potent therapeutic effects over traditional drug development strategies.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :3,348,074
- Total Download :1,746
- Today View :2,236
