FBXW7 Antibodies

Background

FBXW7 is a widely expressed F-box protein in eukaryotic cells, mainly functioning as the substrate recognition subunit of the SCF ubiquitin ligase complex. This gene specifically recognizes and mediates the ubiquitination degradation of various cancer proteins and cell cycle regulatory proteins, thereby playing a core regulatory role in key biological processes such as cell cycle checkpoints, cell growth, and differentiation. Since it was independently identified by multiple research teams in 1999, FBXW7 has received continuous attention due to its significant role in maintaining genomic stability. Mutations in this protein have been proven to be closely related to the occurrence and development of various malignant tumors. In-depth studies on the structure and function of this protein have greatly advanced our understanding of the ubiquitin-proteasome system, the mechanism of tumor occurrence, and targeted treatment strategies.

Structure Function Application Advantage Our Products

Structure of FBXW7

FBXW7 is a F-box protein with a molecular weight of approximately 79 kDa. The specific value may vary slightly among different species and splice variants.

Species	Human	Mouse	Rat
Molecular Weight (kDa)	~79	~78.5	~79.2
Primary Structural Differences	Dimerization domain, F-box, WD40 repeat	Highly conservative	Highly conservative

This protein contains approximately 707 amino acid residues. Its three-dimensional structure is formed by a typical seven-leaf β-spiral structure located at the C-terminal WD40 repeat domain, which is responsible for recognizing and binding to substrates containing specific phosphorylation motifs. The N-terminal F-box domain is responsible for binding to Skp1 protein, thereby anchoring it to the SCF ubiquitin ligase complex. A central hydrophobic pocket and multiple key amino acid residues (such as Arg465, Arg479) jointly form an accurate substrate binding interface, ensuring its specific recognition and ubiquitination marking of key regulatory proteins such as c-Myc and Cyclin E, thereby achieving strict regulation of the cell cycle and proliferation.

Fig. 1 FBXW7 Regulation in the Cell.¹

Key structural properties of FBXW7:

Typical WD40 β-helical propeller domain
Located in the conservative substrate recognition pocket on C
Containing a phosphorylation-dependent binding interface
Key Arg residues ensure substrate specific binding

Functions of FBXW7

The core function of the FBXW7 gene is to act as the substrate recognition subunit of the SCF ubiquitin ligase, mediating the degradation of key regulatory proteins, thereby maintaining cellular homeostasis. However, it is also widely involved in various cellular biological processes.

Function	Description
Cell Cycle Regulation	By targeting and degrading proteins such as Cyclin E and c-Myc, the cell cycle process is precisely controlled, preventing abnormal proliferation.
Tumor Suppression	As a key tumor suppressor gene, its functional inactivation or mutation is directly associated with the occurrence and development of various malignant tumors (such as colorectal cancer, leukemia).
Differentiation and Development	By regulating key proteins in signaling pathways such as Notch and c-Jun, it influences the process of cell differentiation and embryonic development.
Metabolic Regulation	It participates in regulating the stability of metabolic-related pathways such as mTOR, and affects the energy metabolism and growth of cells.
Genome stability	By removing misfolded or damaged proteins, it helps maintain the integrity and stability of the genome.

Corresponding to the hyperbolic oxygen dissociation curve characteristic of myoglobin in the template, the recognition of substrates by FBXW7 relies on its highly specific phosphorylation-dependent mechanism: Only after the specific motifs of its substrate protein (such as Cyclin E) are phosphorylated, can FBXW7 bind to it and initiate ubiquitination degradation, which ensures its precise temporal regulatory role in cellular signal transduction.

Applications of FBXW7 and FBXW7 Antibody in Literature

1. Fan, Jingyi, et al. "Clinical significance of FBXW7 loss of function in human cancers." Molecular cancer 21.1 (2022): 87. https://doi.org/10.1186/s12943-022-01548-2

The article indicates that FBXW7 is a key component of the SCF ubiquitin ligase and regulates cellular processes by degrading various cancer proteins. Its functional inactivation is common in multiple types of cancers such as lung cancer and colon cancer, and is associated with chemotherapy resistance and poor prognosis. The mutation characteristics provide new directions for targeted therapy.

2. Di Fiore, Riccardo, et al. "The role of FBXW7 in gynecologic malignancies." Cells 12.10 (2023): 1415. https://doi.org/10.3390/cells12101415

The article indicates that FBXW7 is a core component of the SCF ubiquitin ligase and exerts tumor-suppressing effects by degrading various cancer proteins. It frequently mutates in multiple gynecological tumors and is associated with poor prognosis and treatment resistance, making it a potential diagnostic marker and therapeutic target.

3. Chen, Siyu, et al. "FBXW7 in breast cancer: mechanism of action and therapeutic potential." Journal of Experimental & Clinical Cancer Research 42.1 (2023): 226. https://doi.org/10.1186/s13046-023-02767-1

The article indicates that FBXW7, as a component of the SCF ubiquitin ligase for substrate recognition, degrades key cancer proteins. Its absence or mutation is associated with the progression of breast cancer and chemotherapy resistance. Studying its mechanism provides an important direction for the development of targeted therapy and new biomarkers.

4. Yeh, Chien-Hung, Marcia Bellon, and Christophe Nicot. "FBXW7: a critical tumor suppressor of human cancers." Molecular cancer 17.1 (2018): 115. https://doi.org/10.1186/s12943-018-0857-2

The article indicates that FBXW7 is a key substrate recognition component of the SCF ubiquitin ligase, and plays an important tumor-suppressing role by degrading various cancer proteins. It frequently undergoes mutations or deletions in multiple human cancers, resulting in functional inactivation and has significant clinical prognostic value.

5. Lan, Huiyin, and Yi Sun. "FBXW7 E3 ubiquitin ligase: degrading, not degrading, or being degraded." Protein & Cell 10.12 (2019): 861-863. https://doi.org/10.1007/s13238-019-0652-x

The article indicates that FBXW7, as the substrate recognition subunit of the SCF ubiquitin ligase, mainly degrades various cancer proteins through K48-linked ubiquitination to exert its tumor-suppressing effect. The study also found that it can functionally regulate through K63-linked ubiquitination of non-classical substrates, or undergo self-degradation, presenting three different modes of action.

Creative Biolabs: FBXW7 Antibodies for Research

Creative Biolabs specializes in the production of high-quality FBXW7 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom FBXW7 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our FBXW7 antibodies, custom preparations, or technical support, contact us at email.

Reference

Fan, Jingyi, et al. "Clinical significance of FBXW7 loss of function in human cancers." Molecular cancer 21.1 (2022): 87. https://doi.org/10.1186/s12943-022-01548-2