Tamoxifen
Tamoxifen is an estrogen analog and is the first example of a
SERM. Tamoxifen shows estrogen-like agonist activity on bone and simultaneously displays estrogen antagonist activity on the breast. An unwanted effect of tamoxifen is its estrogen-like action on the uterus, what may increase the risk of endometrial carcinoma.
TAP1
Transporter Associated with antigen Processing 1 (is induced by NF-kB). TAP belongs to the ABC family of ATP-dependent transporters. It transports peptides (which have been processed in the cytoplasm by the proteasome) into the ER, where the peptides are assembled into ternary complexes wit the alpha and beta2-m chains of the MHC1 for antigen presentation
Tat
Tat is one of the six known regulatory proteins of HIV-1. It is essential for HIV-1 replication, but it also might be involved in other nonimmune and immune dysfunctions during AIDS: Tat is secreted by infected cells and it induces angiogenesis and inflammation (thus contributing to Kaposi's carcinoma). Tat also induces apoptosis in T cells and inhibits T cell proliferation, and it induces the expression of a number of cytokines. Tat was reported to inhibit the killing of tumor targets by NK cells, apparently through blocking granzyme A secretion.
TBP
The TATA-binding protein (TBP) is one of the subunits of the transcription factor TFIID. TBP recognizes the TATA box and facilitates TFIID to bind to the promoter region of a gene. Once TFIID is bound to the promoter, other general transcription factors, along with RNA Pol II, assemble to the transcription complex.
T cell development
T cells develop within the thymus. Common lymphoid progenitors (that also give rise to
B lymphocytes) leave the bone marrow and migrate to the thymus. There, the progenitor cells
closely associate with the epithelial thymic stroma network by which a signal is
transduced through the Notch1 receptor that commits the progenitors to the T cell
lineage. Immature T cells are found within the thymic cortex, whereas more mature
T cells are found within the medulla.
Immature progenitor cells that just enter the thymic cortex lack most of the
surface molecules characteristic of mature T cells and their receptor genes are
not yet rearranged. Interaction with the stroma results in a first signal that leads
to the expression of T cell specific genes, such as CD2 and Thy-1 (in mice).
But at this point they do not express the CD3:T-cell receptor complex nor the
coreceptors CD4 or CD8. At this stage the cells are called double-negative thymocytes.
These immature double-negative T cells correspond to about 60% of all thymocytes that
lack CD4 and CD8. Another 20% of this double-negative pool are cells with rearranged gamma-delta
T cell receptor and the remaining 20% display rearranged alpha-beta T cell receptors
of very limited diversity but which in addition express the NK1.1 receptor (commonly
found on NK cells) and which therefore are called NK T cells.
But back to the double-negative T cells with unrearranged T cell receptor: they give rise
to the development of gamma-delta and alpha-beta T cells. In the alpha-beta pathway,
the double negative thymocytes are distinguished by expression of adhesion molecules
CD44, CD25, and Kit (the receptor of SCF). At first, the cells express Kit and CD44 but
not CD25, and both chains of the T cell receptor are in the germline configuration.
Then expression of CD25 is induced which later results in a decrease of Kit and CD44.
Within those CD44low CD25+ thymocytes, rearrangement of the T cell receptor beta-chain locus occurs.
If rearrangement is not successful, the cells remain in CD44low CD25+ and they eventually die, whereas
cells with rearranged beta-chain lose expression of CD25 again. The rearranged beta-chains pair
with a surrogate pre-T cell receptor alpha chain called pT-alpha, resulting in the formation
of a pre-T-cell receptor which is expressed on the cell surface together with the CD3 molecules.
The pre-T-cell receptor complex leads to proliferation, arrest of further beta-chain gene rearrangements,
and expression of both, CD4 and CD8. Those double-positive thymocytes represent the vast majority of
thymocytes. When the large double-positive thymocytes cease to proliferate, they become small
double-positive cells which rearrange their alpha-chain locus. First, the small double-positive
thymocytes express low levels of the T cell receptor and those that cannot recognize selfpeptide:self-MHC
complexes fail positive selection and die. Those that pass positive selection increase expression
of the T cell receptor and make the decision for being either CD4+ or CD8+ single positive cells.
Thymocytes also undergo negative selection which eliminates those cells that recognize self-antigens.
Only about 2% of all double-positive thymocytes survive this dual screening and mature as single-positive
T cells.
TGF-beta superfamily
Members of the Transforming Growth Factor beta family are cytokines that regulate the proliferation of cells; often they inhibit the cellular proliferation of normal cells.
T helper cells
CD4+ T cells can be divided into different subsets that drive distinct types of immune responses:
T helper 1 (TH1) cells produce interferon-gamma (IFN-gamma) and TNF-alpha and via interaction with
dendritic cells mainly activate cell-mediated immune responses.
T helper 2 (TH2) cells produce interleukin 4 (IL-4), IL-5, IL-10 and IL-13 and via interaction with B cells
mainly drive antibody-mediated responses.
TH17 cells are another subset of T helper cells that produce IL-17, IL-6 and TNF-alpha and are centrally involved in
mediating so called delayed-type hypersensitivity (DTH) reactions that cause tissue damage in conditions such as
experimental autoimmune encephalomyelitis (EAE) (a model for multiple sclerosis) and rheumatoid arthritis.
The differentiation of Th1, TH2 and TH17 cells is dependent on the action of distinct cytokines:
IL-12 drives TH1 cells, IL4 drives TH2 cells and IL-23 drives TH17 cells. Interestingly, in a reciprocal fashion,
the TH1 cytokine IFN-gamma suppresses TH2 differentiation, the TH2 cytokine IL-4 suppresses TH1 differentiation,
and IFN-gamma plus IL-4 suppresses TH17 differentiation.
Therapeutic antibodies
Therapeutic antibodies are monoclonal antibodies that specifically bind cellular target molecules and
thereby inactivate the antigenic target or stimulate the destruction of a cell that carries the antigen.
Thereby, therapeutic antibodies can be effective in destroying tumor cells: Trastuzumab (Herceptin) targets
the receptor tyrosin kinase ErbB2 on breast cancer cells and Rituximab targets the CD20 marker molecule
on B lymphocytes in lymphoma diseases. Therapeutic antibodies are also used in autoimmune conditions,
such as Infliximab (Remicade) which inhibits TNF-alpha signaling.
TNFR family
Tumor Necrosis Factor Receptor family is important in mediating inflammation and cytotoxicity. Members of the TNFR family are the Death Receptors on the cell surface which mediate apoptosis upon stimulation by specific ligands.
More.
TIR
Toll / IL-1R homology domain, an interleukin-1 receptor type 1-like intracellular signalling domain found in Toll receptors.
TNF receptor family
Death receptors belong to the tumor necrosis factor (TNF) receptor
gene superfamily, which is defined by similar, cysteine-rich extracellular
domains. In addition, the death receptors contain a homologous
cytoplasmic sequence termed the "death domain".
Death domains typically enable death receptors to engage the cell's
apoptotic machinery, but in some instances they mediate functions
that are distinct from or even counteract apoptosis.
More...about TNF receptor mediated apoptosis.
TNFR1
TNFR1 is a prominent member of the tumor necrosis factor (TNF) receptor family, which upon activation by its ligand TNF-alpha can induce apoptosis in various cell types. Ligation by TNF-alpha leads to
trimerization of TNFR1 and the association of
the receptors' death domains. Subsequently, an adapter
termed TRADD (TNFR-associated death domain) binds through
its own death domain to the clustered receptor death domains.
TRADD functions as an adapter that recruits several signaling
molecules to the activated receptor: TNFR-associated factor-2
(TRAF2) and receptor-interacting protein (RIP) stimulate
pathways leading to activation of NF-kB and of JNK/AP-1,
whereas FADD mediates activation of apoptosis.
More...
TLR2
Toll-like receptor 2 (TLR2) is a Death Receptor without DD! TLR2 is a receptor of cells of the innate immune system activated by bacterial lipoproteins. Upon ligation, TLR2 recruits the adaptor molecule Myeloid Differentiation Factor 88 (MyD88) which binds to FADD and activates caspase-8 (Antonios et al., 2000, 19(13):3325-36).
Toll
Toll is a gene initially identified by the Nüsslein-Vollhard
in Drosophila to be involved in insect immunity and early
development. Toll is a type 1 transmembrane protein with
extracellular domain rich in leucine repeats and a cytoplasmic
domain with homology to the human IL-1 receptor.
Flies with the Toll mutation proved to have severe defects in
the production of antimicrobial peptides. The ligand for Toll is
spaetzle.
Toll-like receptors (TLRs)
TLRs comprise a family of 11 members of innate immune receptors:
TLR1 is expressed ubiquitously and binds soluble bacterial factors and
Tri-acyl peptides
TLR2 is expressed on the surface and in phagolysosomes
of myeloid cells, mast cells, NK cells as well by mDCs and T cells.
TLR2 binds bacterial lipoproteins, PGN, LTA, LPS as well as
fungal zymosan, viral and parasitic antigens.
TLR3 is expressed intracellularly by mDCs and NK cells and
detects dsRNA, siRNA, shRNA and endogeneous mRNA.
TLR4 is present on the surface of monocytes, mast cells, neutrophils
as well as on T regs and gamma-delta T cells and endothelial cells.
TLR4 recognizes bacterial LPS, viral proteins and endogeneous
proteins such as HSP70, HSP90, fibronectin, fibrinogen...
TLR5 is found on the surface of epithelial and NK cells and mDCs monocytes
and binds bacterial flagellin.
TLR6 is expressed on the surface of myeloid, mast, and B cells and forms
heterodimers with TLR2.
TLR7 is found endosomal in pDCs, in B cells and endophils, binding
viral ssRNA.
TLR8 is found endosomal in NK, T and myeloid cells and binds viral ssRNA.
TLR9 is expressed endosomal by pDCs, B/NK cells, and the surface of
tonsillar cells. TLR9 binds bacterial and viral ssDNA.
TLR10 is found in B cells and pDCs, its ligand is not yet defined.
TLR11 was identified in mouse uroepithelium and identifies a profilin-like
protein of the intracellular protozoan parasite Toxoplasma gondii
(Hopkins and Sriskandan, 2005; Clin. Exp. Immunol., 140: 395-407),
Lauw et al., 2005, Tr. Immunol., 26(10):509-511).
TP53TG1
TP53 target gene 1 (TP53TG1) was identified in a differential display screen using a p53-inducible cell line. TP53TG1 was found to be induced in a p53-dependent manner following cellular stress such as exposure to UV, bleomycin or cis-platin (Takei et al., 1998, Genes Chr. Cancer, 23:1-9).
Tpl-2 kinase
TPL-2 kinase is homologous to NIK. TPL-2 interacts with the C-terminus of NF-kB p105 and mediates phosphorylation of NF-kB p105 (probably not directly but by a downstream kinase). Upon phosphorylation, NF-kB p105 is either totally degraded or only partially degraded from its C-terminus by the proteasome to yield the NF-kB p50 subunit; while the p105 levels are clearly decreased by TPL-2 activity, the p50 levels remain quite constant. The degradation of p105 presumably generates active NF-kB by releasing associated NF-kB/Rel subunits from p105 which can translocate into the nucleus (Belich et al, 1999, Nature, 397: 363-368).
TRADD
TNFR-Associated Death Domain (TRADD) is an adaptor molecule involved in TNFR1-mediated apoptosis pathways.
More...
TRAFs
TNFR-associated factors
Transformation
The process of transformation can be defined as "the introduction of inheritable changes in a cell causing changes in the growth
phenotype and immortalization. Depending on the type and differentiation state of the corresponding cell,
transformation is manifest in a number of ways, including morphological changes, increased saturation density,
loss of contact inhibition, ability to grow in an anchorage-dependent manner or in multiple layers, reduced growth factor
requirement in vitro, and an ability to form tumors upon inoculation into immunodefective hosts.
The accumulation of several transforming events can increase the lifespan of the cell in vitro, occasionally leading to
escape from senescence and the acquisition of unlimited proliferative capacity, commonly referred to as immortalization.
TSP-1
At some point, tumor cells must switch to an angiogenic phenotype in order to satisfy
the necessary supply with nutrients for further growth of the tumor. This switch was found
to coincide with loss of the wild-type allele of p53 and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in cultured fibroblasts from patients with Li-Fraumeni syndrome (Dameron et al., 1994, Science, 265: 1582-4).
Tumo suppressors
Tumor suppressor proteins protect cells from uncontrolled proliferation and
transformation into tumor cells. They affect several cellular pathways, such as those
controlling proliferation, apoptosis, differentiation and genomic identity.
The common definition of a tumor suppressor gene requires the demonstration
of mutations of both copies of a candidate gene in tumors (Knudson's
two-mutation criterion).
TUNEL
Terminal deoxyNucleotidyl (dUTP) transferase-mediated End Labeling. In vivo apoptose assay for the detection of DNA fragmentation in cells.
Type I and type II transmembrane proteins
Transmembrane proteins with their C-terminus residing within the cytoplasm are
type I transmembrane proteins whereas those with their N-terminus exposed to
the cytoplasm are type II transmembrane proteins.