Search results

Overexpression of the HIF1AN is linked with tumor aggressiveness in pancreatic endocrine tumors. HIF1AN hydroxylates Notch ICD at two residues that are crucial for the function of Notch ICD as a transactivator within cells and during neurogenesis and myogenesis. HIF1AN is commonly expressed in invasive breast carcinoma. The hypoxic response and survival recommends that tumour regulation of HIF1AN is an additional important mechanism for HIF pathway activation. HIF1AN is an asparaginyl hydroxylase enzyme that controls the transcriptional activity of hypoxia-inducible factor. FIH1 is a part of the Fe2+ and 2-oxoglutarate-dependent dioxygenase superfamily, FIH1 is protein that hydoxylates a specific asparagine residue (Asn-803) within the HIF1A C-terminal transactivation domain. In normoxia, the HIF1AN-mediated hydroxylation of the HIF1? transactivation domain which results in blockage of the HIF1A-p300/CBP interaction and represses transcriptional activity of HIF1A targeted genes.

IL3 is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders.

TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The 52 kDa Ro protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. Ro/SSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Ribonucleoprotein particle is composed of a single polypeptide and one of four small RNA molecules. The RoSSA is present in all mammalian cells studied but has no known function. At least 2 isoforms are present in nucleated and red blood cells, and tissue specific differences in Ro/SSA proteins were identified.

Interleukin 33 (IL-33) is a 32kDa proinflammatory cytokine that may also regulate gene transcription in producer cells. IL-33 is structurally related to IL-1, which induces helper T cells to produce type 2 cytokines and acts through the receptor IL1RL-1 (IL1 receptor-like-1), which is known also as ST2. Binding of IL-33 to this receptor activates NF-kappa-B and MAP kinases and induces in vitro Th2 cells to produce cytokines. In vivo, IL-33 induces expression of IL-4, IL-5, IL-13 and leads to severe pathological changes in mucosal organs and in vitro, it can be divided to N-terminal fragment of 12kDa and C-terminal fragment of 18kDa by cleavage of caspase-1.

TP53I3 participates in the generation of reactive oxygen species (ROS). TP53I3 has low NADPH-dependent naphtoquinone reductase activity, with a preference for 1,2-naphtoquinone over 1,4-naphtoquinone. TP53I3 has low NADPH-dependent diamine reductase activity (in vitro). TP53I3 is localized to the cytoplasm and induced in primary, non-transformed and transformed cell cultures after exposure to genotoxic agents. TP53I3 microsatellite polymorphism is associated with differential susceptibility to cancer.

Members of the Interferon regulatory factor (IRF) family regulate gene expression critical to immune response, hemopoiesis, and proliferation. IRF-3 is a member of the IRF family, and is distinct from other family members. Its transcriptional activity is regulated solely by posttranslational modifications. It plays a crucial role in activation of innate immunity and inflammation in response to viral infection. IRF-3 mediates interferon-stimulated response element (isre) promoter activation. Functions as a molecular switch for antiviral activity. Dsrna generated during the course of an viral infection leads to IRF3 phosphorylation on the c-terminal serine/threonine cluster. This induces a conformational change, leading to its dimerization, nuclear localization and association with creb binding protein (crebbp) to form dsrna-activated factor 1 (draf1), a complex which activates the transcription of genes under the control of isre. The complex binds to the ie and prdiii regions on the ifn

GDF3 is a member of the TGF-beta superfamily though it does not show similarity pattern of conserved cysteine residues. GDF3 is linked to Vg-1 and human BMP-4. GDF3 transcripts are identified mainly in adult bone marrow, spleen, thymus, and adipose tissue. GDF3 expression is upregulated strongly in high-fat-fed C57Bl/6J FABP4/aP2 null mice, which develop obesity but not the related hyperglycemia or hyperinsulinemia characteristic of type II diabetes. GDF3 expression therefore bonds fatty acid metabolism in adipocytes and the expression of a differentiation regulator belonging to the bone morphogenetic proteins.

The epidermal growth factor receptor (EGF R) subfamily of receptor tyrosine kinases comprises four members: EGF R (also known as HER1, ErbB1 or ErbB), ErbB2 (Neu, HER-2), ErbB3 (HER-3), and ErbB4 (HER-4). All family members are type I transmembrane glycoprotein that has an extracellular domain which contains two cysteine-rich domains separated by a spacer region that is involved in ligand-binding, and a cytoplasmic domain which has a membrane-proximal tyrosine kinase domain and a C-terminal tail with multiple tyrosine autophosphorylation sites. The human EGF R gene encodes a 1210 amino acid (aa) residue precursor with a 24 aa putative signal peptide, a 621 aa extracellular domain, a 23 aa transmembrane domain, and a 542 aa cytoplasmic domain. EGF R has been shown to bind a subset of the EGF family ligands, including EGF, amphiregulin, TGF-a , betacellulin, epiregulin, heparin-binding EGF and neuregulin-2 in the absence of a co-receptor. Ligand binding induces EGF R homodimerization as well as heterdimerization with ErbB2, resulting in kinase activation, tyrosine phosphorylation and cell signaling. EGF R can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGF R signaling has been shown to regulate multiple biological functions including cell proliferation, differentiation, motility and apoptosis. In addition, EGF R signaling has also been shown to play a role in carcinogenesis.

NXT1 operates as a nuclear export factor in both RAN and CRM1 dependent pathways. NXT1 is known to stimulate the export of U1 snRNA in RAN (Ras-related nuclear protein) and CRM1 (chromosome region maintenance) dependent pathways and the export of tRNA and mRNA in a CRM1-independent pathway. This protein heterodimerizes with Tap protein and regulates the ability of Tap protein to intermediate nuclear mRNA export.

Stem cell factor / KIT ligand (SCF) is a cytokine which binds CD117 (c-Kit). SCF is also known as "steel factor" or "c-kit ligand". SCF exists in two forms, cell surface bound SCF and soluble (or free) SCF. Soluble SCF is produced by the cleavage of surface bound SCF by metalloproteases.
SCF is a growth factor important for the survival, proliferation, and differentiation of hematopoietic stem cells and other hematopoietic progenitor cells. One of its roles is to change the BFU-E (burst-forming unit-erythroid) cells, which are the earliest erythrocyte precursors in the erythrocytic series, into the CFU-E (colony-forming unit-erythroid).

Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-?, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established.
Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It has been postulated to play a role in innate immunity.
Visfatin exerts insulin-mimetic effects that are dose-dependent and quantitatively similar to those of insulin in stimulating muscle and adipocyte glucose transport, and in inhibiting hepatocyte glucose production. Intravenous injection of recombinant visfatin in mice decreased plasma glucose in a dose-dependent fashion. In keeping with its insulin-mimetic effects, visfatin was as effective as insulin in reducing hyperglycemia in insulin-deficient diabetic mice. Visfatin was also found to be bound to and activate insulin receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin and insulin did not compete for binding to the insulin receptor, indicating that the two proteins were recognized by different regions of the receptor. Thus, visfatin might play a role in glucose homeostasis and dysregulation in biosynthesis or signal transduction, and might contribute to the pathogenesis of diabetes.

TSSC4 is a member of the TSSC4 family. TSSC4 protein is one of quite a few tumor-suppressing subtransferable fragments found in the imprinted gene domain of 11p15.5, a significant tumor-suppressor gene section. Modifications in this section are linked to the Beckwith-Wiedemann syndrome, rhabdomyosarcoma, Wilms tumor, adrenocortical carcinoma, and breast, ovarian, and lung cancer. TSSC4 takes part in malignancies and disease that include this section in addition to hematopoietic cell function. TSSC4 is broadly expressed in virtually all adult tissues, and is found in fetal liver, brain, lung and kidney.

Vascular endothelial growth factor is an important signaling protein involved in both vasculogenesis and angiogenesis. As its name implies, VEGF activity has been mostly studied on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g. stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells ).VEGF mediates increased vascular permeability, induces angiogenesis, vasculogenesis and endothelial cell growth, promotes cell migration, and inhibits apoptosis. In vitro, VEGF has been shown to stimulate endothelial cell mitogenesis and cell migration. VEGF is also a vasodilator and increases microvascular permeability and was originally referred to as vascular permeability factor.
Elevated levels of this protein is linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). It is produced in two forms, SDF-1?/CXCL12a and SDF-1?/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid. CXCL12 is strongly chemotactic for lymphocytes and has been implicated as an important cell co-ordinator during development. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow. Mice which were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life. As another role, CXCL12a alters also the electrophysiology of neurons. CXCL12 was shown to be expressend in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).
The receptor for this chemokine is CXCR4, which was previously called fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 is also bound by CXCR7 receptor.
The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.

Macrophage Scavenger Receptor 1, also known as MSR1 is a member of the class A macrophage scavenger receptors, which comprises three different types 1, 2 and 3 generated by alternative splicing. Furthermore, these receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological as well as pathological processes which include atherosclerosis, Alzheimer's disease, and host defense.

IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.

GDNF promotes the survival and differentiation of neurons in culture, and is able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung disease.
GDNF enhances survival and morphological differentiation of neurons and increases their high-affinity uptake.

TFAM is a mitochondrial transcription factor which is a main activator of mitochondrial transcription and is also a participant in mitochondrial genome replication. TFAM is situated primarily in the nuclei of elongated spermatids and takes part in the regulation of gene expression of the haploid male genome. TFAM is linked to mitochondrial disorder in humans characterized by ocular myopathy, exercise intolerance and muscle wasting.

Interleukin 10 or IL-10 or human cytokine synthesis inhibitory factor, is a cytokine (anti-inflammatory). IL10 gene is coding for il-10 In humans. Interleukin 10 has a receptor complex that is built from a couple of IL-10 receptor-1 and a couple of IL-10 receptor-2 proteins. therfore, the whole receptor unit consists of four IL-10 receptor molecules. IL-10 binds the receptor and causes STAT3 signalling through the phosphorylation of the cytoplasmic ends of IL-10 receptor 1 and IL-10 receptor 2 through JAK1 and Tyk2.

Binds to tnfrsf13b/taci and tnfrsf17/bcma. tnfsf13/april binds to the same 2 receptors, together, they form a 2 ligands -2 receptors pathway involved in the stimulation of b- and t-cell function and the regulation of humoral immunity. A third b-cell specific baff-receptor (baffr/br3) promotes the survival of mature b-cells and the b-cell response. B Lymphocyte Stimulator functions as a potent B-cell growth factor in costimulation assays. Administration of BAFF Human recombinant to mice disrupts splenic B-cell and T-cell zones and results in elevated levels of serum immunoglobulin.

ATPase inhibitory factor 1 (ATPIF1) attaches to the C-terminal region of a beta subunit of the F1-ATPase at low pH values and, through interference of the beta and gamma subunit interaction, ATPIF1 controls the activity of the F1 (the hydrophilic catalytic core), F0 (the membrane embedded protein channel) ATPase. ATPIF1 overexpression in a number of human carcinomas additionally reinforces its participation in oncogenesis and offers insight into the transformed metabolism of cancer cells, including the reprogramming of energy metabolism in relation to glycolysis. Endogenous F1F(o)-ATPase inhibitor curbing ATP depletion when the mitochondrial membrane potential drops below a threshold and the F1F(o)-ATP synthase begins hydrolyzing ATP to pump protons out of the mitochondrial matrix.

Interleukin-3 is a pleiotropic cytokine produced primarily by activated T cells. IL-3 is thought to function via specific cell surface receptors to stimulate the proliferation, differentiation and survival of haematopoietic cell lines. IL-3 has also been shown to affect the functional activity of a variety of other cell types including mast cells, eosinophils, megakaryocytes and basophils.