we found 129 genes (142 probesets) differentially expressed ......
we found 129 genes (142 probesets) differentially expressed between the control and current MDD groups (FDR<0.1)More...
Positive relationships between PRF1 and other components at different levels (count: 0)
Positive relationship network of PRF1 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between PRF1 and MDD (count: 0)
Negative relationships between PRF1 and other components at different levels (count: 0)
Graft-versus-host disease (GVHD) pathophysiology can be summ......
Graft-versus-host disease (GVHD) pathophysiology can be summerized in a three-step process. During step 1, the conditioning regimen (irradiation and/or chemotherapy) leads to damage, activation of host tissues and induction of inflammatory cytokines secretion. Increased expression of major histocompatibility complex (MHC) antigens and adhesion molecules leads to enhancement of the recognition of host MHC and/or minor histocompatibility antigens by mature donor T cells. Donor T-cell activation in step II is characterized by the predominance of Th1 cells and the secretion of IL-2 and IFN-gamma. These cytokines induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. Lipopolysaccharide (LPS), which leaks through the intestinal mucosa that was damaged during step 1, together with IFN-gamma, from step 2, further stimulate macrophages to secrete cytokines and NO. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.More...
Type I diabetes mellitus is a disease that results from auto......
Type I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-presenting cell (APC), such as macrophages and dendritic cells, and presented in a complex with MHC-II molecules on the surface of the APC. Then immunogenic signals from APC activate CD4+ T cells, predominantly of the Th1 subset. Antigen-activated Th1 cells produce IL-2 and IFNgamma. They activate macrophages and cytotoxic CD8+ T cells, and these effector cells may kill islet beta-cells by one or both of two types of mechanisms: (1) direct interactions of antigen-specific cytotoxic T cells with a beta-cell autoantigen-MHC-I complex on the beta-cell, and (2) non-specific inflammatory mediators, such as free radicals/oxidants and cytokines (IL-1, TNFalpha, TNFbeta, IFNgamma). Type I diabetes is a polygenic disease. One of the principle determining genetic factors in diabetes incidence is the inheritance of mutant MHC-II alleles. Another plausible candidate gene is the insulin gene.More...
Natural killer (NK) cells are lymphocytes of the innate immu......
Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit MHC class I exprssion or alter its conformation. The mechanism of NK cell killing is the same as that used by the cytotoxic T cells generated in an adaptive immune response; cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death.More...
Myocarditis is a cardiac disease associated with inflammatio......
Myocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is still considered the dominant etiological agent. Myocarditis may be caused by direct cytopathic effects of virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. The virus enters the myocyte through internalization of the coxsackie-adenoviral receptor (CAR) and its coreceptor, decay-accelerating factor (DAF). Viral proteases cleave various proteins in the host cell. One example is viral protease 2A, which cleaves eukaryote initiation factor 4G (eIF4G) and the dystrophin protein, resulting in a complete shutdown of cap-dependent RNA translation and cytoskeletal destruction in infected cardiomyocytes, respectively. CVB3 also cleaves the member of the Bcl-2 family Bid, leading to apoptosis. CVB3 infection also induces the cleavage of cyclin D protein through a proteasome-dependent pathway, leading to the host cell-growth arrest. Viral infection and necrosis of myocytes may lead to the release of intracellular antigens, resulting in activation of self-reactive T cells. CVB infection is a significant cause of dilated cardiomyopathy (DCM) as well as myocarditis. Epidemiologically, myocarditis underlies a significant portion of patients with DCM.More...
The classification of autoimmune throid disease (AITD) inclu......
The classification of autoimmune throid disease (AITD) includes Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD) and autoimmune atrophic thyroiditis or primary myxedema. HT is characterized by the presence of goitre, thyroid autoantibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg) in serum and varying degrees of thyroid dysfunction. During HT, self-reactive CD4+ T lymphocytes (Th) recruit B cells and CD8+ T cells (CTL) into the thyroid. Disease progression leads to the death of thyroid cells and hypothyroidism. Both autoantibodies and thyroid-specific cytotoxic T lymphocytes (CTLs) have been proposed to be responsible for autoimmune thyrocyte depletion. In GD, the TSH-R is the most important autoantigen. Antibodies directed against it mimic the effects of the hormone on thyroid cells, TSH, stimulating autonomous production of thyroxine and triiodothyronine and causing hyperthyroidism. The presence of TSH-R-blocking antibodies that bind the TSH receptor in a similar fashion to the antibodies in patients with Graves' disease but that block rather than activate the receptor explains some cases of atrophic hypothyroidism.More...
After transplantation of organ allografts, there are two pat......
After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft.More...
One mechanism used by cytotoxic T cells to kill tumor cells ......
One mechanism used by cytotoxic T cells to kill tumor cells and virus-infected cells is the release of perforin and granzyme proteins. Perforin proteins form pores in the membranes of the attacked cell, allowing the entry of Granzyme A and Granzyme B. Granzyme B induces caspase activation and cleavage of factors like ICAD, releasing DFF40 to fragment DNA, one of the hallmarks of apoptotic cell death. Granzyme A is also an abundant granzyme released by cytotoxic T cells and is important in cytotoxic T cell induced apoptosis, activating caspase independent pathways. Once in a cell, Granzyme A activates DNA nicking by the recently identified DNAse NM23-H1, a tumor suppressor gene product whose expression is reduced in transformed, metastatic cells. The previous identification of NM23-H1 as a tumor suppressor indicates that its DNAse activity plays an important role in immune surveillance to prevent cancer through the induction of tumor cell apoptosis. The activation of NM23-H1 occurs indirectly, through the cleavage of proteins that inhibit NM23-H1 in the SET complex, which includes SET, Ape1, pp32 and HMG2. SET is a substrate for the Granzyme A protease, and SET cleavage relieves NM23-H1 inhibition to cause apoptotic DNA degradation. In addition to inhibiting NM23-H1, SET has nucleosome assembly activity and also may help the interaction of transcriptional regulation with chromatin structure by interacting with the transcriptional coactivator CBP. The targets of Granzyme A found in the SET complex also have other important functions. Ape1 repairs oxidative DNA damage, reduces transcription factors involved in immediate early responses, and its cleavage by Granzyme A may contribute to DNA degradation and apoptosis. HMG2 is an acidic chromatin-associated protein that bends DNA, alters chromatin structure and alters the accessibility of genes for transcription. In addition to acting as a nucleosome assembly factor and an inhibitor of NM23-H1, SET inhibits DNA and histone methylation by the CBP transcriptional coactivator. The tumor suppressor pp32 is not cleaved by Granzyme A but is part of the SET complex. Other targets of Granzyme A include nuclear lamins responsible for maintaining nuclear structure and histones, the basic building blocks of chromatin structure. The common involvement of the proteins of the SET complex in chromatin structure and DNA repair suggest that they work together to protect chromatin and DNA structure and that inactivation of the complex contributes to apoptosis by blocking the maintenance of DNA and chromatin structural integrity.More...
Cytotoxic T lymphocytes (CTLs), also known as killer T cells......
Cytotoxic T lymphocytes (CTLs), also known as killer T cells, provide a cell-mediated response to specific foreign antigens associated with cells. CTLs only respond to foreign antigen when it is presented bound to the MHC-1 expressed on the surface of all cells. CTLs do not respond to soluble antigen, but induce apoptosis in viral-infected cells and in cancer cells. When the complex of antigen bound to MHC-1 is bound to antigen-specific T cell receptor, the cytotoxic T cell induces apoptosis in the target cell primarily by two pathways, one involving perforin-mediated apoptosis and the other involving Fas/Fas-ligand interaction. When CTLs are activated by recognition of specific antigen on a cell, they release perforin proteins that integrate into the membrane of the target cell and organize to form a membrane pore. This allows the protease granzyme to enter the cell and activate the apoptotic caspase proteolytic cascade , and also allows other molecules to cross the cell membrane and trigger osmotic lysis of the membrane. The interaction of T-cell Fas ligand with the Fas receptor in the target cell can also activate the caspase cascade and other pathways involved in apoptosis. The interaction of a CTL with antigen-MHC I complex activates the CTL to proliferate and amplify the clone of T cells that respond to that antigen, amplifying the immune response against that specific antigen.More...
Apoptosis, programmed cell death, is triggered by a variety ......
Apoptosis, programmed cell death, is triggered by a variety of stimuli, including cell surface receptors like FAS, mitochondrial response to stress, and cytotoxic T cells. Caspases are a class of cysteine proteases that includes several representatives involved in apoptosis. The caspases convey the apoptotic signal in a proteolytic cascade, with caspases cleaving and activating other caspases that then degrade other cellular targets that lead to cell death. The caspases at the upper end of the cascade include caspase-8 and caspase-9. Caspase-8 is the initial caspase involved in response to receptors with a death domain like FAS. The mitochondrial stress pathway begins with the release of cytochrome c from mitochondria, which then interacts with Apaf-1, causing self-cleavage and activation of caspase-9. Caspase-3, -6 and-7 are downstream caspases that are activated by the upstream proteases and act themselves to cleave cellular targets. Granzyme B and perforin proteins released by cytotoxic T cells induce apoptosis in target cells, forming transmembrane pores, and triggering apoptosis, perhaps through cleavage of caspases, although caspase-independent mechanisms of Granzyme B mediated apoptosis have been suggested.More...
D4-GDI (GDP dissociation inhibitor) is a negative regulator ......
D4-GDI (GDP dissociation inhibitor) is a negative regulator of the ras related Rho Family of GTPases. Since the rho GTPases promote cytoskeletal and membrane changes associated with apoptotic cell death, the removal of the D4-GDI block through its cleavage is important for inducing apoptosis. Caspase-3 cleaves the 28 kDa mature form of D4-GDI to give a 5 kDa and 23 kDa Size fragment. The 23 kDa fragment then translocates to the nucleus. The mechanisms involving cleavage of D4-GDI with apoptosis are not presently known. Activation of the Jun N-Terminal kinase, a regulator of apoptosis, may be one of the mechanisms.More...
PRF1 related Reactome pathways (count: 0)
PRF1 related interactors from protein-protein interaction data in HPRD (count: 3)
Basic Information
Positive relationships between PRF1 and other components at different levels (count: 0)
