TNFSF9

TNFSF9
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2X29
Identifiers
Aliases	TNFSF9, 4-1BB-L, CD137L, TNLG5A, tumor necrosis factor superfamily member 9, TNF superfamily member 9
External IDs	OMIM: 606182; MGI: 1101058; HomoloGene: 55782; GeneCards: TNFSF9; OMA:TNFSF9 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 6,531,026 bp[1] End 6,535,924 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 D Start 57,412,325 bp[2] End 57,414,757 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell testicle internal globus pallidus vagina Brodmann area 9 right frontal lobe upper lobe of left lung prefrontal cortex muscle of thigh cerebellar hemisphere Top expressed in gastrula decidua blastocyst embryo embryo cumulus cell humerus ventricular zone medial ganglionic eminence stroma of bone marrow More reference expression data BioGPS n/a
Gene ontology Molecular function tumor necrosis factor receptor binding cytokine activity signaling receptor binding tumor necrosis factor receptor superfamily binding Cellular component integral component of membrane membrane extracellular space plasma membrane Biological process cell-cell signaling cell population proliferation immune response signal transduction apoptotic process positive regulation of activated T cell proliferation positive regulation of cytotoxic T cell differentiation tumor necrosis factor-mediated signaling pathway regulation of signaling receptor activity regulation of T cell proliferation regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8744 21950 Ensembl ENSG00000125657 ENSMUSG00000035678 UniProt P41273 P41274 RefSeq (mRNA) NM_003811 NM_009404 RefSeq (protein) NP_003802 NP_033430 Location (UCSC) Chr 19: 6.53 – 6.54 Mb Chr 17: 57.41 – 57.41 Mb PubMed search [3] [4]
Wikidata
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Tumor necrosis factor ligand superfamily member 9 also known as 4-1BB ligand or 4-1BBL or CD137L is a protein that in humans is encoded by the TNFSF9 gene.^[5]

4-1BBL is a type 2 transmembrane glycoprotein receptor that is found on APCs (antigen presenting cells) and binds to 4-1BB (also known as CD137). The 4-1BB/4-1BBL complex belongs to the TNFR:TNF superfamily,^[6] which is expressed on activated T Lymphocytes.^[7]

Structure of 4-1BB/4-1BBL complex

The 4-1BB/4-1BBL complex consists of three monomeric 4-1BBs bound to a trimeric 4-1BBL. Each 4-1BB monomer binds to two 4-1BBLs via cysteine-rich domains (CRDs). The interaction between 4-1BB and the second 4-1BBL is required to stabilize their interactions.^[8] The link with 4-1BBL is largely made up of amino acids from the dynamic loops of the CRD2 and the β sheet of CRD3 of 4-1BB, according to a detailed study of the binding between the 4-1BB and 4-1BBL interface. CRD2 amino acids (T61, Q67, and K69) interact with the AA′ loop (Y110 and G114) and the intra-H-strand loop (Q227 and Q230) of 4-1BBL to form various hydrogen bond interactions.^[9]

Application to cancer immunotherapy

Studies on the poorly immunogenic Ag104A sarcoma and the extremely tumorigenic P815 mastocytoma provided the first systematic proof that anti-4-1BB antibodies have potent anti-tumor effects. Anti-4-1BB administration to mice with the aforementioned tumors was shown to substantially inhibit tumor growth by increasing CTL activity. In the years to come, more studies verified and legitimized the effect of 4-1BB signaling to inhibit tumor growth.^[10]

The interaction between 4-1BB and 4-1BBL provide costimulatory signals to a variety of T cells, which can be used to discover cancer immunotherapy. The 4-1BB/4-1BBL complex together with a signal provided by a T-cell receptor can provide costimulatory signals to CD4⁺ and CD8⁺ T cells in mice, leading to the activation of CD4⁺ and CD8⁺ T cells. The activation of CD8⁺ T cells is essential in antitumor immunity.^[6] The 4-1BB/4-1BBL complex with the help of T-cell receptor signals can co-stimulate human CD28⁻ T cells and trigger the increase in CD28⁻ T cells. Unlike the activation of CD8⁺ T cells, the proliferation of CD28⁻ T cells can negatively affect cancer state and other diseases. Therefore, this pathway can be targeted for immunotherapy.^[11]

See also

• CD137

References

External links

• 4-1BB+Ligand at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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