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STAT1 is a member of the Signal Transducers and Activators of Transcriptionfamily of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type Ior type IIinterferons. In response to IFN-?stimulation, STAT1 forms homodimers or heterodimers with STAT3that bind to the GAS (Interferon-Gamma Activated Sequence) promoter element; in response to either IFN-? or IFN-?stimulation, STAT1 forms a heterodimer with STAT2that can bind the ISRE (Interferon Stimulated Response Element) promoter element. In either case, binding of the promoter element leads to an increased expression of ISG (Interferon Stimulated Genes).

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

Herpesvirus entry mediator or HVEM or tumour necrosis factor receptor superfamily member 14 or TNFRSF14, is part of the TNF receptors family that is a receptor located on the cell surface. The cytoplasmic area of this receptor can bind all sorts of TNF receptor associated factor (TRAF) protein. Those proteins can mediate pathways activating an immune response. The MITF is regulating TNFRSF14 gene expression.

Fibroblast growth factor 18 (FGF18) is a member of the large FGF family which has at least 23 members. FGF18 is a growth factor with a core 120 amino acid FGF domain which allows for a common tertiary structure. FGFs are expressed in the course of the embryonic development and in restricted adult tissues. FGF-18 is an indispensable regulator of long bone and calvarial development. FGF-18 signals via FGFR 1c, 2c, 3c, and 4.

GDF-11 belongs to the bone morphogenetic protein (BMP) family and the TGF-beta superfamily. GDF-11 is a central developmental factor which controls muscular and neural development. In adults, GDF-11 encourages cardiac hypertrophy reverse by the revival of cardiomyocytes.

L-threonine to glycine degradation consists of a two-step biochemical pathway which involvs the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is initially converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. Glycine C-Acetyltransferase (GCAT) is the 2nd enzyme in this pathway, which subsequently catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The GCAT enzyme is regard as a class II pyridoxal-phosphate-dependent aminotransferase. GCAT is strongly expressed in the heart, brain, liver and pancreas. GCAT is also found in lung.

Antioxidant enzyme Glutathione S- Transferase (GST) is thought to do the primary cellular defense mechanism against reactive oxygen species. GST reduces lipid hydroperoxides through its Se-independent glutathione peroxidase activity. The enzyme also detoxifies lipid peroxidation end products such as 4-hydroxynonenal (4-HNE).
The soluble GST is a 26 kDa protein which occurs as a dimer in all aerobic organisms. Each monomer has two domains, one that binds GSH and is an /-structure similar to thioredoxin and the other, all helical, that binds the hydrophobic substrate. The GST -fusion protein expression system is a widely used recombinant protein expression system that allows a peptide or a regulatory protein domain to be expressed as a fusion to the C-terminus of Schistosoma japonicum GST. Fusion proteins also possess GST -enzymatic activity and can undergo dimerization similar to in vivo. The fusion protein can be purified via GST -affinity column chromatography. In most cases, the desired peptides or domains are removed from GST by applying a specific protease that recognizes and cleaves the linker between the protein domain and GST. The technique has been widely used to generate different kinds of proteins for crystallization, molecular immunology studies, the production of vaccines and studies involving protein-protein and protein-DNA interactions.

GSTP1 is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are believed to function in xenobiotic metabolism and have a part in susceptibility to cancer, and other diseases. GSTP1 is a glutathione S-transferase belonging to the pi class. GST family enzymes play a significant role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based upon the biochemical, immunologic and structural properties of the soluble GSTs they are grouped into 4 main classes: alpha, mu, pi, and theta. The GSTP1 enzyme acts by catalyzing the reaction of glutathione with an acceptor molecule to form a Sulfur-substituted glutathione. The reactions employing glutathione contribute the transformation of a broad range of electrophiles, including reactive products of lipid, protein, carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress.
The GSTP1 inactivation through CpG hypermethylation is frequent in pituitary adenomas and may be a factor in aggressive pituitary tumor behavior. GSTP1 is may be a transcriptional target of the p53 tumor suppressor gene. Single-nucleotide polymorphism in GSTP1 is linked to modified protein binding, which influence GSTP1's contribution to carcinogen and drug metabolism, and possibly disease pathogenesis and/or drug response. GST-pi might have central roles in proliferation of androgen-independent human prostate cancer cells.

GSTT1 belongs to a superfamily of proteins which catalyze the conjugation of reduced glutathione to a variety of electrophilic and hydrophobic compounds. GSTT1 is one of the GSTs’ four main classes: alpha, mu, pi and theta (which includes GSTT1 and GSTT2). GSTT1 is involved in activation and detoxification reactions and catalyzes the conjugation of industrial chemicals, such as epoxybutane, ethylene oxides, halomethane with glutathione. GSTT1 is found in erythrocytes, at low levels in the liver as well as in Clara and ciliated cells at the alveolar/bronchiolar junction in the lung.
The GSTT1 gene is deficient in 38% of the population. The GSTTI enzyme deficiency might influence the individual risk for development of acquired aplastic anemia and acute myeloid leukemia. The presence or absence of the GSTT1 gene is concurrent with GSST1+ (the conjugator) and GSTT1- (the non-conjugator) phenotypes correspondingly. The GSTT1+ phenotype is able to catalyze the glutathione conjugation of dichloromethane. GSTT1-null genotypes are seen as having a higher risk of developing leukoplakia. Germline genetic polymorphism in GSTT1 is linked to breast cancer.

GSTZ1 is part of the glutathione S-transferase super-family which encodes multifunctional enzymes vital in the detoxification of electrophilic molecules, including carcinogens, mutagens, and several therapeutic drugs, by conjugation with glutathione. GSTZ1 participates in the catabolism of phenylalanine and tyrosine. Thus defects in GSTZ1 cause harsh metabolic disorders including alkaptonuria, phenylketonuria and tyrosinaemia. GSTZ1 is a bifunctional protein which has minimal glutathione-conjugating activity with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. GSTZ1 has low glutathione peroxidase activity with T-butyl and cumene hydroperoxides. GSTZ1 catalyzes the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid.

Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family if type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1to -4 are known. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

CEBPB is an intronless gene and its protein is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. CEBPB can also form heterodimers with the related proteins CEBP-alpha, CEBP-delta, and CEBP-gamma. CEBPB is important in the regulation of genes involved in immune and inflammatory responses and has been shown to bind to the IL-1 response element in the IL-6 gene, as well as to regulatory regions of several acute-phase and cytokine genes. In addition, CEBPB can bind the promoter and upstream element and stimulate the expression of the collagen type I gene.

Acidic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis.
Three alternatively spliced variants encoding different isoforms have been described.
The hep-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

PDGF-AA, PDGF-BB and PDGF-AB, are potent mitogens for a variety of cell types including smooth muscle cells, connective tissue cells, bone and cartilage cells, and some blood cells. The PDGF is stored in platelet alpha-granules and released upon platelet activation. The PDGF is involved in a number of biological processes, including hyperplasia, chemotaxis, embryonic neuron development, and respiratory tubule epithelial cell development. Two distinct signaling receptors used by PDGF have been identified and named PDGFR-alpha and PDGFR-beta. PDGFR-alpha is high-affinity receptor for each of the three PDGF forms. On the other hand, PDGFR-beta interacts with only PDGF-BB and PDGF-AB.

Acidic fibroblast growth factor is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Three alternatively spliced variants encoding different isoforms have been described. The binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.

MGAT2 is an enzyme which takes part in the catalyzation of a crucial step in the reaction of oligomannose which converts to complex N-glycans. MGAT2 has three domains, classic to glycosyltransferase: short N-terminal cytoplasmic domain, a C-terminal catalytic domain and hydrophobic non-cleavable signal-anchor domain. The enzyme MGAT2 is encoded by the MGAT2 gene in humans. There are no introns in the DNA coding the gene, therefore mutations in the MGAT2 will result in carbohydrate-deficient glycoprotein syndrome, type II.

Gltathione S-transferase PI 2, also known as GSTP2 is multifunctional enzyme which is involved in theprotection of cellular components against anti-cancer drugs or peroxidative stress. Furthermore, down regulation of GSTP2induces an increase of oxidative damage in the pyramidal cells of the CA1&CA3 regions as well as in the granular layer ofthe dentate gyrus, which at the end leads to structural and functional damage.

Transforming growth factor betas (TGFBetas) mediate many cell-cell interactions that occur during embryonic development. Three TGFBetas have been identified in mammals. TGFBeta1, TGFBeta2 and TGFBeta3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecule. This antibody reacts with the precursor and mature form of TGFBeta2 and to a lesser extent TGFBeta3, but does not cross react with TGFBeta1.

GMCSF is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13.
GM-CSF stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

SUMF1 is a member of the SUMF family. SUMF1 catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue called C-alpha-formylglycine. Alterations in this gene result in multiple sulfatase deficiency which is a lysosomal storage disorder.

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. TNF is mainly secreted by macrophages.
TNF causes apoptotic cell death, cellular proliferation, differentiation, inflammation, tumorigenesis and viral replication, TNF is also involved in lipid metabolism, and coagulation. TNF's primary role is in the regulation of immune cells.
Dysregulation and, in particular, overproduction of TNF have been implicated in a variety of human diseases- autoimmune diseases, insulin resistance, and cancer.

HDAC2 is a member of the histone deacetylase family that performs through the construction of large multiprotein complexes and are in charge of the deacetylation of lysine residues on the N-terminal region of the core histones. HDAC2 forms transcriptional repressor complexes by relating to a diversity of proteins, like YY1- a mammalian zinc-finger transcription factor.
In addition, HDAC2 has a vital part in transcriptional regulation, cell cycle progression and developmental procedures.

The FGFs are a family of more than 20 small (~17–26 kDa) secreted peptides. The initial characterization of these proteins focused on their ability to stimulate fibroblast proliferation. This mitogenic activity was mediated through FGF receptors (FGFRs) 1, 2, or 3. A fourth closely related tyrosine kinase receptor (FGFR4) was able to bind the FGFs but did not lead to a mitogenic response.
FGFs modulate cellular activity via at least 5 distinct subfamilies of high-affinity FGF receptors (FGFRs): FGFR-1, -2, -3, and -4, all with intrinsic tyrosine kinase activity and, except for FGFR-4, multiple splice isoforms, and FGFR-5, which lacks an intracellular kinase domain. There is growing evidence that FGFRs can be important for regulation of glucose and lipid homeostasis. The overexpression of a dominant negative form of FGFR-1 in cells leads to diabetes in mice, which thus implies that proper FGF signaling is required for normal ? cell function and glycemia maintenance. FGFR-2 appears to be a key molecule during pancreatic development. Moreover, FGFR-4 has been implicated in cholesterol metabolism and bile acid synthesis.
FGF-19, has been shown to cause resistance to diet-induced obesity and desensitization and to improve glucose, and lipid profiles in diabetic rodents. Since these effects, at least in part, are mediated through the observed changes in metabolic rates, FGF-19 can be considered as a regulator of energy expenditure.
FGF-21 is preferentially expressed in liver, but an exact knowledge of FGF-21 bioactivity and its mode of action have been lacking to date. FGF-21 is a potent activator of glucose uptake on adipocytes, protects animals from diet-induced obesity when overexpressed in transgenic mice, and lowers blood glucose and triglyceride levels when therapeutically administered to diabetic rodents.

TNFSF12 is a cytokine that is part of the TNF ligand family. TNFSF12 is a ligand for the FN14/TWEAKR receptor. TNFSF12 has overlapping signaling functions with TNF, but displays a much wider tissue distribution. TNFSF12 induces apoptosis through multiple pathways of cell death in a cell type-specific manner. TNFSF12 promotes proliferation and migration of endothelial cells, and therefore acts as a regulator of angiogenesis. TNFSF12 is expressed in adult heart, pancreas, skeletal muscle, small intestine, spleen and peripheral blood lymphocytes. TWEAK h induces NFkB and chemokine secretion. TNFSF12 exerts an apoptotic activity in HT-29 human adenocarcinoma cells whilst cultured in the presence of IFN-?. TNFSF12 promotes proliferation and migration of endothelial cells.