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tumor necrosis factor β (TNF-β) 722 tumor necrosis factor (TNF) family
NH 2
COOH
Cys
69
Cys
101
Molecular model of a TNF-α (cachectin) human recombinant form.
Resolution = 2.6 Å. The molecule exists as a trimer in which the three subunits
are related by approximately threefold symmetry.
(HIV) or other pathogenic microorganisms. It can induce
anorexia that may lead to death from malnutrition. Both
TNF-α and TNF-β are cytotoxic for tumor cells but not normal
cells. TNF induces vascular endothelial cells to express
new adhesion molecules, induces macrophages and endothelial
cells to secrete chemokines, and facilitates apoptosis of
target cells. Large amounts of TNF produced during severe
infections may lead to systemic effects that include fever,
synthesis of acute phase proteins by the liver, and cachexia.
Very large quantities of TNF may induce intravascular
thrombosis and shock. Of all its biological effects, the cytotoxic
effects of TNF-α and its induction of apoptosis are the
most important. Its specific receptor is tumor necrosis factor
receptor (TNFR). TNF has powerful immunoregulatory,
cytotoxic, antiviral and procoagulatory properties. It may
facilitate cell survival and affects hematopoiesis.
tumor necrosis factor (TNF-)
A 25-kDa protein synthesized by activated lymphocytes.
It can kill tumor cells in culture, induce expression of
genes, stimulate proliferation of fibroblasts, and mimic
most of the actions of TNF-α (cachectin). It participates
in inflammation and graft rejection and was previously
TNF receptors. Resolution = 2.85 Å.
termed lymphotoxin. TNF-β and TNF-α have approximately
equivalent affinities for TNF receptors. Both 55- and
80-kDa TNF receptors bind TNF-β. TNF-β has diverse
effects that include killing some cells and causing proliferation
of others. It is the mediator whereby cytolytic T cells,
natural killer cells, lymphokine-activated killer cells, and
helper–killer T cells induce fatal injuries to their targets.
TNF-β and TNF-α have been suggested to play a role in
acquired immune deficiency syndrome (AIDS), possibly
contributing to its pathogenesis.
tumor necrosis factor (TNF) family
Tumor necrosis factor (TNF) is responsible for lipopolysaccharide
(LPS)-induced hemorrhagic necrosis of tumors
in animals. It was subsequently identified as cachectin, a
factor responsible for wasting during parasitic infections
or neoplasia. TNF cDNA cloning and purification of TNF
protein showed that TNF is related structurally to lymphotoxin,
a product of activated T lymphocytes called LTα
(formerly TNF-β). The TNF designation now refers to what
was formerly TNF-α. Both TNF and LTα are synthesized
by different cells. They occupy the same receptors and can
produce similar biological activities. LTα forms a heterocomplex
with LTβ. This complex requires a different
receptor (LTβ receptor) and performs biologic functions
different from those of LTα alone. TNF and LTα are the
first described members of the large TNF family of ligands
and receptors that also includes LTβ, the Fas/Apol receptor
and its ligand, TRAIL/Apo2L and its receptor, CD40, and
many others.