SPARC is a key factor in cell-matrix interactions and possibly tumour aggressiveness. The SPARC gene, which encodes a multifunctional glycoprotein with roles in tissue development, remodelling and fibrosis. A regulator of cell-extracellular matrix (ECM) interactions, SPARC represents a major factor in the ECM remodelling occurring during tumour invasion. in silico analysis reveals 4 UTR-SNPs located in the 3 -UTR of the SPARC gene, corresponding to 1474 g a, 1551 g c, 1922 t g and 2072 c t changes, which are significantly associated with tumoral state of the tissue. Of all hits, the 2072 SPARC polymorphism had the best association with cancer._x000B__x000B_SPARC therefore is a gene involved in a number of diseases including rheumatoid arthritis, scleroderma, tumor development and metastasis. SPARC variants have been detected in tumour samples of patients with acute myeloblastic leukemia (AML).

SPARC is a key factor in cell-matrix interactions and possibly tumour aggressiveness. The SPARC gene, which encodes a multifunctional glycoprotein with roles in tissue development, remodelling and fibrosis. A regulator of cell-extracellular matrix (ECM) interactions, SPARC represents a major factor in the ECM remodelling occurring during tumour invasion. in silico analysis reveals 4 UTR-SNPs located in the 3 -UTR of the SPARC gene, corresponding to 1474 g a, 1551 g c, 1922 t g and 2072 c t changes, which are significantly associated with tumoral state of the tissue. Of all hits, the 2072 SPARC polymorphism had the best association with cancer._x000B__x000B_SPARC therefore is a gene involved in a number of diseases including rheumatoid arthritis, scleroderma, tumor development and metastasis. SPARC variants have been detected in tumour samples of patients with acute myeloblastic leukemia (AML).

SPARC is a key factor in cell-matrix interactions and possibly tumour aggressiveness. The SPARC gene, which encodes a multifunctional glycoprotein with roles in tissue development, remodelling and _x000B_fibrosis. A regulator of cell-extracellular matrix (ECM) interactions, SPARC represents a major factor in the ECM remodelling occurring during tumour invasion. in silico analysis reveals 4 UTR-SNPs located in the 3 -UTR of the SPARC gene, corresponding to 1474 g a, 1551 g c, 1922 t g and 2072 c t changes, which are significantly associated with tumoral state of the tissue. Of all hits, the 2072 SPARC polymorphism had the best association with cancer._x000B__x000B_SPARC therefore is a gene involved in a number of diseases including rheumatoid arthritis, scleroderma, tumor development and metastasis. SPARC variants have been detected in tumour samples of patients with acute myeloblastic leukemia (AML).

NHE-1 is involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. NHE-1 plays an important role in signal transduction. Located in the kidney and intestine.

NHE-1 is involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. NHE-1 plays an important role in signal transduction. Located in the kidney and intestine.

NHE-1 is involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. NHE-1 plays an important role in signal transduction. Located in the kidney and intestine.

SMO is a G protein-coupled receptor (GPCR) that putatively associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. The binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). In basal cell carcinoma there are two somatic mutations SMO, D473-> H473 and R562 ->Q562.

SMO is a G protein-coupled receptor (GPCR) that putatively associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. The binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). In basal cell carcinoma there are two somatic mutations SMO, D473-> H473 and R562 ->Q562.

SMO is a G protein-coupled receptor (GPCR) that putatively associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. The binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). In basal cell carcinoma there are two somatic mutations SMO, D473-> H473 and R562 ->Q562.

Structural Maintenance of Chromosomes (SMC) family proteins play critical roles in various nuclear events that require structural changes of chromosomes, including mitotic chromosome organization, DNA recombination and repair and global transcriptional repression. The chromosome proteins are conserved in eukaryotes lead to mitotic chromosome segregation defects, suggesting a critical function of SMC family proteins in mitotic chromosome dynamics. _x000B_SMC1 and SMC3 form a heterodimeric complex required for metaphase progression in mitotic cells. Specifically this SMC1/SMC3 complex is responsible for sister chromatid cohesion during metaphase. A number of cellular factors interact with hSMC1/hSMC3 during cell cycle. The major population of hSMC1/hSMC3 is in a compex with hRAD21 forming the human cohesion complex. Human cohesion associates with chromosomes which peaks at S phase and dissociates from chromosomes during G2/M transition. In addition, a subpopulation of hSMC1/hSMC3 associates tightly with nuclear matrix and centrosomes during interphase. A subset of hSMC1/hSMC3 is localized to spindle poles, spindles and kinetochores during mitosis when cohesin is in the cytoplasm. hSMC1/hSMC3 is required for spindle aster formation in vitro and reacts with nuclear mitotic apparatus (2) protein in vivo.

Novel adaptor protein which mediates the activation of sphingomyelinase by receptors such as tumor necrosis factor receptor type 1 and CD40 and subsequent apoptosis in cardiomyocytes. Inhibition of this factor may provide a novel intervention point for reducing ischemia/reperfusion injury.

Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4

Ubiquitin-like protein which can be covalently attached to target lysines as a monomer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4

Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins. Interacts with EPHA2, VAV1, LCP2 and PDGFRB. The C-terminal domain is essential for the homodimerization and the interaction with CBL. While the interaction with CBL is apparently mediated via the hydrophobic region of this domain, the highly charged region is apparently required for the homodimerization. Expressed in lung and fetal brain. Weakly expressed in heart, adult brain, placenta, liver, skeletal muscle, kidney and pancreas.

Sirtuin 1 (Sirt 1) is encoded by a gene that encodes a number of the sirtuin-like proteins, all homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain. Yeast sirtuin proteins are known to regulate epigenetic gene silencing, suppress recombination of DNA and repressess rDNA transcription by the RNA pol. Studies suggest that the human sirtuins regulate apoptosis by impairing proapoptotic ability and modulating cell senescence. They regulate muscle differentiation by deacetylating key proteins. They also deacetylate the following: 'Lys-382' of p53/TP53, TAF1B, 'Lys-266' of SUV39H1 (leading to its activation), 'Lys-26' of HIST1H1E, APEX1 at 'Lys-6' and 'Lys-7' and 'Lys-16' of histone H4 (in vitro), as well as H2A. Sirtuins are also involved in HES1- and HEY2-mediated transcriptional repression and inhibit skeletal muscle differentiation by deacetylating PCAF and MYOD1. They may serve as a sensor of the cytosolic ratio of NAD+/NADH, which is essential in skeletal muscle cell differentiation. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the case of HIV-1 infection, sirtuin interacts with and deacetylates the viral Tat protein. Cellular AP endonuclease activity is stimulated by promoting the association of APEX1 to XRCC1. Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as observed in yeast.

Seven in absentia homolog 1 (SIAH-1) is a member of the RING-finger-containing E3 ubiquitin ligases. Alpha-synuclein and synphilin-1 are substrates of SIAH-1. Both proteins are involved in the development of Parkinson's disease (PD). Mutations in Parkin, another E3 ubiquitin ligase which ubiquinates synphilin-1 and glycosylated alpha-synuclein, have been defined as a major cause of autosomal recessive PD. The role of SIAH-1 in PD is highlighted by the fact that SIAH-1 is a component of the Lewy bodies and plays a role in apoptosis caused by nitric oxide (NO) induced oxidative stress. _x000B__x000B_Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) a classic glycolytic enzyme, and multi-functional protein. GAPDH plays role as a mediator for cell death. GAPDH translocates to the nucleus under a variety of stressors/conditions, most of which are associated with oxidative stress. Sequential steps lead to nuclear translocation of GAPDH during cell death; 1] a catalytic cysteine in GAPDH (C150 in rat GAPDH) is S-nitrosylated by nitric oxide (NO) which is generated from inducible nitric oxide synthase (iNOS) and/or neuronal NOS (nNOS); 2] the modified GAPDH becomes capable of binding with Siah1, an E3 ubiquitin ligase, and stabilizes it;3] the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity.

Seven in absentia homolog 1 (SIAH-1) is a member of the RING-finger-containing E3 ubiquitin ligases. Alpha-synuclein and synphilin-1 are substrates of SIAH-1. Both proteins are involved in the development of Parkinson's disease (PD). Mutations in Parkin, another E3 ubiquitin ligase which ubiquinates synphilin-1 and glycosylated alpha-synuclein, have been defined as a major cause of autosomal recessive PD. The role of SIAH-1 in PD is highlighted by the fact that SIAH-1 is a component of the Lewy bodies and plays a role in apoptosis caused by nitric oxide (NO) induced oxidative stress. _x000B__x000B_Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) a classic glycolytic enzyme, and multi-functional protein. GAPDH plays role as a mediator for cell death. GAPDH translocates to the nucleus under a variety of stressors/conditions, most of which are associated with oxidative stress. Sequential steps lead to nuclear translocation of GAPDH during cell death; 1] a catalytic cysteine in GAPDH (C150 in rat GAPDH) is S-nitrosylated by nitric oxide (NO) which is generated from inducible nitric oxide synthase (iNOS) and/or neuronal NOS (nNOS); 2] the modified GAPDH becomes capable of binding with Siah1, an E3 ubiquitin ligase, and stabilizes it;3] the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity.

Recognizes a protein of ~50kDa, which is identified as the SH2-containing protein-tyrosine phosphatase 1 (SHP-1). This antibody is highly specific to SHP-1 and shows no cross-reaction with other protein-tyrosine phosphatase. SHP-1 is known to play a crucial role in the regulation of hematopoiesis and it regulates the transcriptional activity stimulated by the erythropoietin (EPO)-induced JAK/STAT and MAPK pathways and is involved in the signaling machinery responsible for erythroid differentiation and suppression of apoptosis. Furthermore, the observation that SHP-1 associates with RAFTK/Pyk2/CAK activated by beta-chemokine receptor (CCR5) and SHP-1 also associates with the adaptor protein Grb2 and the Src-related kinase Syk indicates the role of SHP-1 in modulating cell migration, proliferation, and immune functions.

SLAM (Signaling Lymphocyte-Activation Molecule) is a glycosylated type-I transmembrane protein which is present on the surface of B and T cells. SLAM is a high-affinity self-ligand which, when triggered, co-activated B or T lymphocyte responses and is considered to be important in bi-directional T - B cell stimulation. SAP (SLAM-Associated Protein) has been determined to be a 15 kDa protein. SAP is believed to the genetic defect which cauases X-linked Lymphoproliferative Syndrome (XLP). SAP is thought to bind to SLAM by the SH2 domain of the SAP protein. Binding of SAP to the SLAM protein blocks the binding of SHP-2 to the phosphorylated SLAM protein which causes XLP.

Human SET was originally identified as part of the SET-CAN fusion gene produced by a somatic translocation event in a patient with acute undifferentiated leukemia. In developing kidney, SET is highly expressed in the zone of nephron morphogenesis. SET has been shown to be a potent and specific inhibitor of protein phosphatase 2A, a family of major serine/threonine phosphatases involved in regulating cell proliferation and differentiation. SET is also involved in the regulation of renal cell proliferation and tumorigenesis. SET mRNA expression is markedly reduced in cells rendered quiescent by serum starvation, contact inhibition, or differentiation. SET protein expression is also much greater in developing rat and human kidney than in fully differentiated, mature kidney. High levels of SET mRNA and SET protein expression arefound in Wilms' tumor, but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma.