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TNFRSF17

What is TNFRSF17?

TNFRSF17, also known as B cell maturation antigen (BCMA or BCM), is a member of the TNF receptor superfamily, is encoded by the TNFRSF17 gene. Most of the members of the TNF receptor superfamily are type I transmembrane proteins. The extracellular domain has a conserved cysteine-rich domain, and can transmit cellular stimulation signals through protein-protein interaction to regulate different physiological functions of cells, such as cell activation, proliferation, transformation, survival, apoptosis and death.

TNFRSF17 can promote B cell survival and play a role in humoral immune regulation. In addition, it can activate NF-kappa-B and JNK.

The Structure of TNFRSF17

TNFRSF17 gene is located on chromosome 16p13, which encodes a protein composed of 184amino acid residues. Its intracellular region contains 80 amino acid residues, which can interact with TRAF (TNFR-associated factor) 1, 2 and 3, and activate TRAF-dependent NF-κB, JNK and p38 MAPK pathways. Its extracellular domain has a conserved cysteine-rich domain and can transmit cell stimulation signals through protein-protein interaction.

The Expression of TNFRSF17

TNFRSF17, expressed on the surface of B lymphocytes and plasma cells, is a marker protein for the maturation of B lymphocytes and plays an important role in B cell maturation and autoimmune response.

The expression of TNFRSF17 was detected in spleen, thymus, bone marrow and heart, and lower levels were detected in kidney and lung.

In addition, it is highly expressed in malignant proliferative B lymphocytes (such as myeloma cells, leukemia cells).

TNFRSF17 ligand

TNFRSF17 ligands include BAFF (B cell activators, also known as TALL-1, BLyS or TNFSF13B) and APRIL (TNFSF13).

These two ligands belong to type Ⅱ transmembrane proteins and have 30% sequence homology between them. APRIL is mainly secreted by osteoclasts and can directly promote the survival of malignant plasma cells through proteoglycan. BAFF is mainly expressed by monocytes, macrophages, dendritic cells and other immune cells.

The Function of TNFRSF17

The binding of TNFRSF17 with ligand can activate NF-κB signal pathway and JNK signal pathway, which plays an important role in autoimmune diseases and humoral immunity.

TNFRSF17 mediates the physiological processes related to cell differentiation and growth by binding to TRAF protein and activating signal transduction molecules such as p38, c-jun, Elk and NF-κB.

The binding of TNFRSF17 to its ligand BAFF plays an important role in the maintenance of long-term survival of bone marrow plasma cells.

TNFRSF17 is also closely related to the proliferation of B cells.

TNFRSF17 plays an important role in maintaining the survival of plasma cells.

Applications of TNFRSF17 in Treatment

TNFRSF17, is only expressed in plasma cells, it is not expressed in natural and memory B cells, and it plays a key role in cell survival, proliferation, metastasis and drug resistance. These characteristics make it a target for immunotherapy, especially for the treatment of multiple myeloma.

The new tumor immunotherapy methods for BCMA mainly include CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy therapy), bispecific antibody (BsAb) and antibody drug conjugate (ADC)).

At present, the drug research targeting BCMA is mostly aimed at multiple myeloma, and it is still in the stage of clinical research.

The application of drug Belantamab mafodotin in the study of multiple myeloma, the research code is GSK-2857916, is currently in clinical phase Ⅲ.

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TNFRSF17 Proteins

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