Product Includes | Product # | Quantity | Mol. Wt | Isotype/Source |
---|---|---|---|---|
CRBN (D8H3S) Rabbit mAb | 71810 | 20 µl | 55 kDa | Rabbit IgG |
CUL4A Antibody | 2699 | 20 µl | 80, 82 kDa | Rabbit  |
DDB-1 (D4C8) Rabbit mAb | 6998 | 20 µl | 127 kDa | Rabbit IgG |
RBX1 (D3J5I) Rabbit mAb | 11922 | 20 µl | 13 kDa | Rabbit IgG |
NEDD8 (19E3) Rabbit mAb | 2754 | 20 µl | 9 kDa | Rabbit IgG |
Ubiquitin (E4I2J) Rabbit mAb | 43124 | 20 µl | Rabbit IgG | |
Anti-rabbit IgG, HRP-linked Antibody | 7074 | 100 µl | Goat  |
Please visit cellsignal.com for individual component applications, species cross-reactivity, dilutions, protocols, and additional product information.
Description
The CRL4/CRBN Targeted Protein Degradation Complex Antibody Sampler Kit provides an economical means of detecting the individual components of a CRL4/CRBN E3 ubiquitin ligase complex, including free and conjugated forms of both NEDD8 and ubiquitin. The kit includes enough antibodies to perform two western blot experiments with each primary antibody.
Storage
Background
Targeted protein degradation is an experimental method of drug-based protein targeting that leverages endogenous proteolysis machinery, such as the the ubiquitin proteasome system (UPS), to selectively degrade proteins of interest (POIs). It is being actively explored as a therapeutic strategy to target and degrade POIs that contribute to disease progression (1). This approach differs from traditional small-molecule therapeutics that seek to suppress disease proteins (e.g., kinases) by sterically blocking catalytic domains. Proteolysis-targeting chimeras (PROTACs) and "molecular glue" degraders are the two primary degrader modalities used in UPS-mediated targeted protein degradation. PROTACs are bivalent, chemically-linked ligands that induce proximity between a POI and an E3 ubiquitin ligase, resulting in ubiquitination of the target protein, and its subsequent degradation by the UPS (2,3). Molecular glues are molecules that chemically generate novel interaction surfaces between two proteins, which can used to induce proximity between a POI and an E3 ligase. Cereblon (CRBN) is the substrate-recognition component of a Cullin-RING-ubiquitin (E3) ligase complex (CRL4/CRBN) that was among the first to be recognized for its therapeutic potential via targeted protein degradation (4). The CRL4/CRBN complex is comprised of CRBN, DDB-1, RBX1, and the scaffold protein CUL4A; its ligase activity is dynamically regulated via the covalent modification (neddylation) of CUL4A by NEDD8 (5). In unrelated mechanistic studies of multiple myeloma drugs, it was revealed that phthalimides (e.g., thalidomide, lenalidomide) promoted CRBN-dependent recruitment, ubiquitination, and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) (6). The discovery that phthalimides were functioning as molecular glue degraders that could selective degrade what were previously considered "undruggable" targets, led to a rapid acceleration and expansion of research into targeted protein degradation, with the promise of novel therapies for diseases deemed largely intractable using conventional small-molecule therapies (7-9).
- Bond, M.J. and Crews, C.M. (2021) RSC Chem Biol 2, 725-742.
- Sakamoto, K.M. et al. (2001) Proc Natl Acad Sci U S A 98, 8554-9.
- Sakamoto, K.M. et al. (2003) Mol Cell Proteomics 2, 1350-8.
- Krönke, J. et al. (2014) Science 343, 301-5.
- Hofmann, H. et al. (2013) J Virol 87, 11741-50.
- Lu, G. et al. (2014) Science 343, 305-9.
- Shirasaki, R. et al. (2021) Cell Rep 34, 108532.
- Alabi, S.B. and Crews, C.M. (2021) J Biol Chem 296, 100647.
- Alabi, S. et al. (2021) Nat Commun 12, 920.
Background References
Trademarks and Patents
Limited Uses
Except as otherwise expressly agreed in a writing signed by a legally authorized representative of CST, the following terms apply to Products provided by CST, its affiliates or its distributors. Any Customer's terms and conditions that are in addition to, or different from, those contained herein, unless separately accepted in writing by a legally authorized representative of CST, are rejected and are of no force or effect.
Products are labeled with For Research Use Only or a similar labeling statement and have not been approved, cleared, or licensed by the FDA or other regulatory foreign or domestic entity, for any purpose. Customer shall not use any Product for any diagnostic or therapeutic purpose, or otherwise in any manner that conflicts with its labeling statement. Products sold or licensed by CST are provided for Customer as the end-user and solely for research and development uses. Any use of Product for diagnostic, prophylactic or therapeutic purposes, or any purchase of Product for resale (alone or as a component) or other commercial purpose, requires a separate license from CST. Customer shall (a) not sell, license, loan, donate or otherwise transfer or make available any Product to any third party, whether alone or in combination with other materials, or use the Products to manufacture any commercial products, (b) not copy, modify, reverse engineer, decompile, disassemble or otherwise attempt to discover the underlying structure or technology of the Products, or use the Products for the purpose of developing any products or services that would compete with CST products or services, (c) not alter or remove from the Products any trademarks, trade names, logos, patent or copyright notices or markings, (d) use the Products solely in accordance with CST Product Terms of Sale and any applicable documentation, and (e) comply with any license, terms of service or similar agreement with respect to any third party products or services used by Customer in connection with the Products.