Tumor necrosis factors
Encyclopedia
Tumor necrosis factors (or the TNF-family) refers to a group of cytokines family that can cause cell death (apoptosis
). The first two members of the family to be identified were:
All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognized by their specific receptors. Strong hydrogen bonds between the monomers stabilizes the tertiary structure. One such example is the Asn34-Arg82 hydrogen bond in the M. musculus TNF alpha. The PROSITE pattern for this family is located in a beta-strand in the central section of the protein that is conserved across all members.
All members of the TNF family, with the exception of the secreted lymphotoxin and a proliferation-inducing ligand (APRIL), are type II transmembrane proteins which protrude from immune cells. Such membrane-bound TNF ligands frequently signal back to the immune cells when they contact and bind their cognate receptors on other cells.
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
). The first two members of the family to be identified were:
- Tumor necrosis factor-alpha (TNF-α) is the best-known member of this class, and sometimes referred to when the term "tumor necrosis factor" is used. TNF-α is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers. Both the mature protein and a partially-processed form of the hormone can be secreted after cleavage of the propeptide.
- Tumor necrosis factor-beta (TNF-β), also known as lymphotoxinLymphotoxinLymphotoxin is a lymphokine cytokine.It is a protein that is produced by Th1 type T-cells and induces vascular endothelial cells to change their surface adhesion molecules to allow phagocytic cells to bind to them.Lymphotoxin is homologous to Tumor Necrosis Factor beta, but secreted by T-cells...
is a cytokine that is inhibited by interleukin 10Interleukin 10Interleukin-10 , also known as human cytokine synthesis inhibitory factor , is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene....
Family members
Nineteen cytokines have been identified as part of the TNF family on the basis of sequence, functional, and structural similarities. They include:- Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) is a cytokine that has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; it can stimulate cell proliferation and induce cell differentiation under certain conditions.
- Lymphotoxin-alphaLymphotoxin alphaLymphotoxin-alpha is a protein that in humans is encoded by the LTA gene.- Function :Lymphotoxin alpha, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. LTA is highly inducible, secreted, and exists as homotrimeric molecule. LTA forms heterotrimers with...
(LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes that are cytotoxic for a wide range of tumor cells in vitro and in vivo. - T cell antigen gp39 (CD40LCD154CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells , which leads to many effects depending on the target cell type...
), a cytokine that seems to be important in B-cell development and activation. - CD27LCD70CD70 is a ligand for CD27.-External links:...
, a cytokine that plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells. - CD30L, a cytokine that induces proliferation of T cells.
- FASLFAS ligandFas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.- Structure :Fas ligand or...
, a cytokine involved in cell death. - 4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.
- OX40LOX40LOX40L is the ligand for CD134 and is expressed on such cells as DC2s enabling amplification of Th2 cell differentiation. OX40L has also been designated CD252 .-External links:...
, a cytokine that co-stimulates T cell proliferation and cytokine production. - TNF-related apoptosis inducing ligand (TRAILTRAILIn the field of cell biology, TNF-related apoptosis-inducing ligand , is a protein functioning as a ligand that induces the process of cell death called apoptosis. TRAIL has also been designated CD253 .- Gene :...
), a cytokine that induces apoptosis.
All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognized by their specific receptors. Strong hydrogen bonds between the monomers stabilizes the tertiary structure. One such example is the Asn34-Arg82 hydrogen bond in the M. musculus TNF alpha. The PROSITE pattern for this family is located in a beta-strand in the central section of the protein that is conserved across all members.
All members of the TNF family, with the exception of the secreted lymphotoxin and a proliferation-inducing ligand (APRIL), are type II transmembrane proteins which protrude from immune cells. Such membrane-bound TNF ligands frequently signal back to the immune cells when they contact and bind their cognate receptors on other cells.
Examples
Human proteins containing this domain include:- CD40LGCD154CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells , which leads to many effects depending on the target cell type...
; CD70CD70CD70 is a ligand for CD27.-External links:...
; EDAEDA (gene)Ectodysplasin-A is a protein that in humans is encoded by the EDA gene.-Further reading:...
; FASLGFAS ligandFas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.- Structure :Fas ligand or...
; LTALymphotoxin alphaLymphotoxin-alpha is a protein that in humans is encoded by the LTA gene.- Function :Lymphotoxin alpha, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. LTA is highly inducible, secreted, and exists as homotrimeric molecule. LTA forms heterotrimers with...
; LTB; - TNFSF4OX40LOX40L is the ligand for CD134 and is expressed on such cells as DC2s enabling amplification of Th2 cell differentiation. OX40L has also been designated CD252 .-External links:...
; TNFSF5CD154CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells , which leads to many effects depending on the target cell type...
; TNFSF7CD70CD70 is a ligand for CD27.-External links:...
; TNFSF8CD153CD153 is a ligand for CD30....
; TNFSF9; TNFSF10TRAILIn the field of cell biology, TNF-related apoptosis-inducing ligand , is a protein functioning as a ligand that induces the process of cell death called apoptosis. TRAIL has also been designated CD253 .- Gene :...
; TNFSF11RANKLReceptor activator of nuclear factor kappa-B ligand , also known as tumor necrosis factor ligand superfamily member 11 , TNF-related activation-induced cytokine , osteoprotegerin ligand , and osteoclast differentiation factor , is a protein that in humans is encoded by the TNFSF11 gene.RANKL is...
; TNFSF12TNFSF12Tumor necrosis factor ligand superfamily member 12 is a protein that in humans is encoded by the TNFSF12 gene.-Further reading:...
; TNFSF13TNFSF13Tumor necrosis factor ligand superfamily member 13 also known as a proliferation-inducing ligand is a protein that in humans is encoded by the TNFSF13 gene. TNFSF13 has also been designated CD256 .- Function :The protein encoded by this gene is a member of the tumor necrosis factor ligand ...
; TNFSF13BB-cell activating factorB-cell activating factor also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFLSF13B gene...
; TNFSF14TNFSF14Tumor necrosis factor ligand superfamily member 14 is a protein that in humans is encoded by the TNFSF14 gene. TNFSF14 has also been designated as CD258, as well as LIGHT.-Interactions:...
; TNFSF15Vascular endothelial growth inhibitorVascular endothelial growth inhibitor is an anti-angiogenic protein. It belongs to tumor necrosis factor superfamily, where it is member 15. TNFSF15 is the human gene for it.-Gene:-Further reading:...
; TNFSF18TNFSF18Tumor necrosis factor ligand superfamily member 18 is a protein that in humans is encoded by the TNFSF18 gene.-Further reading:...
; - TWEAKTNFSF12Tumor necrosis factor ligand superfamily member 12 is a protein that in humans is encoded by the TNFSF12 gene.-Further reading:...
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