Journal
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
Volume 96, Issue 6, Pages 189-203Publisher
JAPAN ACAD
DOI: 10.2183/pjab.96.016
Keywords
thalidomide; lenalidomide; immunomodulatory imide drugs (IMiDs); cereblon ubiquitin; proteolysis targeting chimeras (PROTACs)
Categories
Funding
- MEXT/JSPS KAKENHI [17H06112, 17H04213, 18H05502]
- PRESTO
- JST [JPMJPR1531]
- Grants-in-Aid for Scientific Research [17H06112, 17H04213, 18H05502] Funding Source: KAKEN
Ask authors/readers for more resources
Thalidomide, originally developed as a sedative drug, causes multiple defects due to severe teratogenicity, but it has been re-purposed for treating multiple myeloma, and derivatives such as lenalidomide and pomalidomide have been developed for treating blood cancers. Although the molecular mechanisms of thalidomide and its derivatives remained poorly understood until recently, we identified cereblon (CRBN), a primary direct target of thalidomide, using ferrite glycidyl methacrylate (FG) beads. CRBN is a ligand-dependent substrate receptor of the E3 ubiquitin ligase complex cullin-RING ligase 4 (CRL4(CRBN)). When a ligand such as thalidomide binds to CRBN, it recognizes various 'neosubstrates' depending on the shape of the ligand. CRL4(CRBN) binds many neosubstrates in the presence of various ligands. CRBN has been utilized in a novel protein knockdown technology named proteolysis targeting chimeras (PROTACs). Heterobifunctional molecules such as dBET1 are being developed to specifically degrade proteins of interest. Herein, we review recent advances in CRBN research.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available