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Leukemia Inhibitory Factor Receptor Alpha or LIFR is a protein, part of the Interleukin-6 receptor group of proteins. As such, LIFR acts as a mediator for various proteins (IL-6, IL-11, IL-27, Oncostatin M etc). LIFR has many functions as a cytokine, he has an affect on the cell proliferation, differentiation and survival in the different stages of life. In different types of breast cancer LIFR is down regulated, and as such, can be used as a prognostic tool.

EIF1AX is an important eukaryotic translation initiation factor. EIF1AX is essential for the binding of the 43S complex (a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5'' end of capped RNA. EIF1AP1 is needed for maximal rate of protein biosynthesis. EIF1AX increases ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA (I) to 40 S ribosomal subunits.

Bcl2 modifying factor, is a member of the Bcl2 protein family of apoptosis mediators. Bcl2 modifying factor is widely expressed in many tissues.
Bcl2 modifying factor contains a single Bcl2 homology domain 3 (BH3), and binds Bcl2 proteins and functions as an apoptotic activator. Also, Bcl2 modifying factor is important for histone deacetylase (HDAC) inhibitors which alters the balance between acetylation and deacetylation, significantly increasing histone acetylation, while strongly inducing apoptosis in a variety of cancer cell types. Bcl2 modifying factor supports Bim in regulating cell death processes in response to many stimuli. A synergistic role for bim and Bcl2 modifying factor in an apoptotic pathway leading to the clearance of Neisseria gonorrhoeae -infected cells.

Leukemia inhibitory factor receptor (LIFR) is the receptor for leukemia inhibitory factor, a pleiotropic cytokine affecting the differentiation, survival, and proliferation of various cells in the adult and the embryo. LIFR plays an imperative role in a number of aspects of early pregnancy such as blastocyst implantation in the uterus.

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.

Leukemia Inhibitory Factor also called LIF is a lymphoid factor that promotes long-term maintenance of embryonic stem cells by suppressing spontaneous differentiation. Leukemia Inhibitory Factor has several functions such as cholinergic neuron differentiation, control of stem cell pluripotency, bone & fat metabolism, mitogenesis of factor dependent cell lines & promotion of megakaryocyte production in vivo. Human and mouse LIF exhibit a 78% identity in its amino acid sequence.

Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signaling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation.
Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occuring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was first characterized as a growth factor that supports the in-vitro colony formation of granulocytes-macrophages progenitor cells. It is a pleiotropic cytokine and a member of a family of endogenous cytokines of the hematopoietic system. GM-CSF is produced as a response to immune or inflammatory stimuli by activated cells of the hematopoietic system such as T cells, B cells, macrophages, mast cells and also fibroblasts and alveolar epithelial cells. It plays an important role in regulating the proliferation, differentiation, survival and activation of hematopoietic cells such as granulocytes and monocytes ,neutrophiles, basophiles and eosonophoiles, erythroid cells, megakaryocytes and T cells.
Human and mouse GM-CSF have about 56% homology and are species specific. Human GM-CSF is not active on mouse cells and vice versa. It is active on canine and feline cells.
GMCSF is 144 amino acids, 22kDa glycoprotein. It is composed of four bundles alpha helices. Its receptor is heterodimers with a ligand-specific alpha subunit and a betac subunit that is shared with the interleukin IL-3 and IL-5 receptors. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors. Cross-linking the two receptor subunits is required for receptor activation and signaling .
GMCSF has been shown to be involved in maturation, mobilization and antigen presentation of myeloid dentritic cells (DCs) in-vivo or ex-vivo. This function promotes Th1 immune responses, cytotoxcity, anti-angiogenesis as well as allergic inflammation, and the development of autoimmunity. Therefore GMCSF can be used in immunotherapy for the treatment of immune suppressed and immune-compromised patients as well as in veterinary medicine for the same purpose. GM-CSF is also important in regulation of embryo development and pregnancy and specifically in embryo implantation and subsequent development .

Fucosyltransferase 7 (FUT7) is a golgi stack membrane protein which is involved in the creation of sialyl-Lewis X antigens. The FUT7 protein leads the synthesis of the E-selectin-binding sialyl-Lewis X moiety. FUT7 catalyzes alpha-1,3 glycosidic linkages involved in the expression of sialyl Lewis X antigens.

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 lymphotoxin-beta which anchors lymphotoxin-alpha to the cell surface. LTA mediates a large variety of inflammatory, immunostimulatory, and antiviral responses. LTA is also involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis.

General Transcription Factor IIF Polypeptide 2 (GTF2F2) is a general transcription initiation factor which binds to RNA polymerase II and helps engage it in the initiation complex in collaboration with TFIIB. GTF2F2 promotes transcription elongation. GTF2F2 shows ATP-dependent DNA-helicase activity.

The clinical use of the potent anti-tumor activity of TNF-a has been limited by the proinflammatory side effects including fever, dose-limiting hypotension, hepatotoxicity, intravascular thrombosis, and hemorrhage. Designing clinically applicable TNF-a mutants with low systemic toxicity has been an intense pharmacological interest. Human TNF-a, which binds to the murine TNF-R55 but not to the mouse TNF-R75, exhibits retained anti-tumor activity and reduced systemic toxicity in mice compared with murine TNF-a, which binds to both murine TNF receptors. Based on these results, many TNF-? mutants that selectively bind to TNF-R55 have been designed. These mutants displayed cytotoxic activities on tumor cell lines in vitro, and exhibited lower systemic toxicity in vivo.
Recombinant Human TNF-a Variant/Mutant compared with the wild-type, has an amino acid sequence deletion from a.a. 1-7, and the following a.a. substitutes Arg8, Lys9, Arg10 and Phe157 which is proven tohave more activity and with less inflammatory side effect in vivo.

Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Once the alternative pathway is activated it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which connects with C3b to form the alternative pathway C3 convertase. Also, Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation.

Excess adiposity is the most important risk in the development of type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-a, and IL-6, that modulate sensitivity and appear to play an important role in the pathogenesis, diabetes, dyslipidemia, inflammation, and atherosclerosis. 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 mimetic effects that are dose-dependent and quantitatively similar to 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 mimetic effects, visfatin was as effective in reducing hyperglycemia in deficient diabetic mice. Visfatin was also found to be bound to and activate receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin did not compete for binding to the 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.

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.

TCEAL3 belongs to the transcription elongation factor A (SII)-like (TCEAL) gene family. TCEAL family members hold TFA domains and operate as nuclear phosphoproteins which control transcription in a promoter context-dependent fashion. Various family members are situated in the X chromosome.

Eukaryotic Translation Initiation Factor 3F, also known as EIF3F belongs to the eIF-3 subunit F family. EIF3F is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which isessential for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosomeand facilitates the recruitment of eIF-1, eIF-1A, eIF 2: GTP: methionyl-tRNAi and eIF-5 to form the 43S preinitiationcomplex (43S PIC). In addition, the eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA forAUG recognition. The eIF-3 complex is also necessary for disassembly and recycling of post termination ribosomalcomplexes and subsequently prevents premature union of the 40S and 60S ribosomal subunits prior to initiation. Among the diseases associated with EIF3F are intrahepatic cholangiocarcinoma, and cholangiocarcinoma.

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/ macrophagemigration, 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 mitogenesisand 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 are linked to POEMS syndrome, also known as Crow-Fukase syndrome. Mutations in this gene have been associated with proliferative and nonproliferative diabetic retinopathy.

The term ‘PDGF’ refers to a family of disulphide bond-linked dimeric isoforms that act as autocrine and paracrine growth factors and are produced by a variety of cell types other than platelets.
They act as potent mitogens for almost all mesenchymally-derived cells. Aberrant expression is involved in certain cancers, fibroproliferative disorders and atherosclerosis. The protein also contributes to wound healing and neural regeneration. There are four members of the PDGF family – PDGF A, PDGF B, PDGF C and PDGF D. Two distinct types of PDGF-A exist – a short form that is soluble and a long form that is retained by the extracellular matrix.

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, and cancer.

VEGF-C, also known as Vascular Endothelial Growth Factor Related Protein (VRP), is a recently discovered VEGF growth factor family member that is most closely related to VEGF-D. Human VEGF-C cDNA encodes a pre-pro-protein of 416 amino acids residues. It is almost identical to the mouse VEGF-C protein. Similar to VEGF-D, VEGF-C has a VEGF homology domain spanning the middle third of the precursor molecule and long N- and C-terminal extensions. In adults, VEGF-C is highly expressed in heart, placenta, ovary and small intestine. Recombinant human VEGF-C, lacking the N- and C-terminal extensions and containing only the middle VEGF homology domain, forms primarily non-covalently linked dimers. This protein is a ligand for both VEGFR-2/KDR and VEGFR-3/FLT-4. Since VEGFR-3 is strongly expressed in lymphatic endothelial cells, it has been postulated that VEGF-C is involved in the regulation of the growth and/or differentiation of lymphatic endothelium. Although recombinant human VEGF-C is also a mitogen for vascular endothelial cells, it is much less potent than VEGF-A.

Transcription Elongation Factor A (SII)-Like 7 (TCEAL7) has a role in the negative regulation of NF-kappa-B signaling at the basal level by controlling transcriptional activity of NF-kappa-B on its target gene promoters. TCEAL7 links with cyclin D1 promoter containing Myc E-box sequence and transcriptionally inhibits cyclin D1 expression. TCEAL7 regulates telomerase reverse transcriptase expression and telomerase activity in both alternative lengthening of telomeres (ALT) and telomerase-positive cell lines. TCEAL7 is highly expressed in normal and fetal brain tissues, and weakly expressed in the uterus and ovary. TCEAL7 is down-regulated in epithelial ovarian, cervical, prostate, breast, brain and lung cancer cell lines and in the brain and ovarian tumors.

Human TNFRSF10A is a type 1 transmembrane protein in the TNF R superfamily. TNFRSF10A is not expressed in rodents. The trimeric ligand Trail binds TNFRSF10A and induces apoptosis, and recombinant, soluble forms of the receptor inhibit Trail-induced apoptosis. TNFRSF10A is expressed generally in damaged, infected, and malignant cells. TNFRSF10A functions in immune surveillance, inducing apoptosis in cancer cells but not normal cells.