DcR3/TNFRSF6B Protein, Human (sf9, hFc)

DcR3 is a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, recognized as a significant anti-apoptotic factor with prominent involvement in various inflammatory and neoplastic conditions. DcR3 can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL against apoptosis^[1][2][3]. DcR3 has been associated with tumorigenesis and metastasis, via DcR3/STAT1/IRF1 feedback loop^[4][5]. DcR3/TNFRSF6B Protein, Human (sf9, hFc) has a full length of 300 amino acids (M1-H300), produced in sf9 insect cells with C-terminal hFc-tag.

Decoy Receptor 3 (DcR3), a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, neutralizes three different TNF ligands/pro-apoptotic molecules: FasL, LIGHT, and TL1A. Each of these ligands engages unique signaling receptors which direct distinct and critical immune responses. Dcr3 has competitive binding with the functional receptors to the respective cytokines (Fas for FasL, DR3 for TL1A, and LTbR and herpesvirus entry mediator/HVEM for LIGHT), thus preventing downstream pro-apoptotic signaling. DcR3 is encoded by the Tnfrsf6b gene, which does not encode a cytoplasmic or transmembrane segment, resulting in an obligate secreted protein of 300 amino acids including the signal peptide. However, mouse and rat genomes lack a Tnfrsf6b gene^[1][2]. DcR3 is overexpressed in a wide variety of malignancies and is correlated with tumorigenesis and progression. Therefore, it has been considered a potential biomarker to predict cancer invasion and progression of inflammation. Specifically, DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in human colorectal cancer (CRC)^[3][4]. In addition, it increases the expression levels of several components of the PI3K/AKT/GSK-3β/β-catenin signaling pathway, such as p-AKT, GSK-3β, p-GSK-3β and β-catenin. Additionally, DcR3 also enhances the expression of N-cadherin and Vimentin and decreases the expression of E-cadherin^[3]. DcR3 also promotes proliferation and invasion of pancreatic cancer via a DcR3/STAT1/IRF1 feedback loop. It promotes the phosphorylation of signal transducers and activators of transcription 1 (STAT1), leading to a dramatic increase in interferon regulatory factor 1 (IRF1). IRF1 then increased the transcriptional activity of DcR3, forming a positive feedback loop to reinforce DcR3 expression^[5]. The homology of human DcR3 protein is low with that of other animals, and the sequence similarity with rats, mice and pigs is 20.49%, 20.82% and 20.00%, respectively.

Measured by its ability to inhibit Fas Ligand induced apoptosis of Jurkat human acute T cell leukemia cells and the ED₅₀ for this effect is typically ≤25 μg/mL in the presence of 200 ng/mL human Fas ligand.

Human

Sf9 insect cells

C-hFc

O95407 (V30-H300)

8771  [NCBI]

Approximately 65 kDa

Greater than 85% as determined by reducing SDS-PAGE.

Solution

Supplied as a 0.2 μm filtered solution of 100 mM Glycine, 10 mM NaCl, pH 7.0.

<1 EU/μg, determined by LAL method.

N/A.

Stored at -80°C for 1 year. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Zhan C, et al. Decoy strategies: the structure of TL1A:DcR3 complex. Structure. 2011 Feb 9;19(2):162-71.  [Content Brief]

  [2]. Lagou S, et al. The Role of Decoy Receptor DcR3 in Gastrointestinal Malignancy. Cancer Diagn Progn. 2022 Jul 3;2(4):411-421.  [Content Brief]

  [3]. Ge H, et al. DcR3 induces proliferation, migration, invasion, and EMT in gastric cancer cells via the PI3K/AKT/GSK-3β/β-catenin signaling pathway. Onco Targets Ther. 2018 Jul 19;11:4177-4187.  [Content Brief]

  [4]. Liu YP, et al. DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC. Oncotarget. 2016 Nov 22;7(47):77306-77318.  [Content Brief]

  [5]. Gao L, et al. DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin. Oncotarget. 2017 Dec 28;9(13):10934-10944.  [Content Brief]