| basic FUNCTION
| mediating osteoclastogenesis and bone loss through systemic activation of T cells |
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activating the antiapoptotic serine threonine kinase AKT/PKB through a signal complex involving TRAF6 and SRC  |
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regulating lymph node organogenesis lymphocyte development and interactions between T cells and dendritic cells |
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key osteoclast differentiation/activation factor through induction of FOSL1 |
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a dentritic cell survival factor, maintaining bone homeostasis through C-FOS-dependent induction of IFNB |
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regulating the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor(CSF1), but other costimulatory signals ITAM-dependent cooperate for bone homeostasis |
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playing an important role in cell migration and the tissue-specific metastatic behaviour of cancer cells |
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inducing the expression of NFATC1, but not of NFKB subunits during osteoclast formation |
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key regulator of bone remodeling, mammary gland formation, lymph node development and T-cell/dendritic cell communication (cooperating with TNFRSF11A) |
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playing a role during heart valve development |
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stimulating osteoclasts and their precursors to release VEGF-C through an NF-kappaB-dependent mechanism |
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an important role in cell migration and the tissue-specific metastatic behaviour of cancer cells |
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controls regulatory T-cell numbers via activation of dendritic cells |
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a key role in female thermoregulation and the central fever response in inflammation |
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controls the incidence and onset of progestin-driven breast cancer |
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a potential role for TNFSF11 inhibition in the management of proliferative breast disease |
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up-regulated CKB mRNA expression and protein production during osteoclastogenesis |
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play a key role in osteoclastogenesis and tumor metastasis |
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induces histone acetyltransferases-mediated NFATC1 acetylation and stability, and subsequently increases the transcriptional activity of NFATC1 during osteoclast differentiation |
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key factor linking bone formation to resorption during bone remodeling |
CELLULAR PROCESS
| cell life, proliferation/growth
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| cell life, antiapoptosis
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| PHYSIOLOGICAL PROCESS
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development
, immunity/defense
, ossification
|
| text
| a key factor for osteoclast differentiation and activation |
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skeletal development and maintenance |
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positive control of cell proliferation |
| signaling
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signal transduction
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| TNFSF11/TNFRSF11A signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover |
| a component
| involvement of the TNFRSF11A/TNFSF11/TNFRSF11B axis in osteosarcoma biology |
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crucial role for the TNFSF11/NFATC1 signaling pathway in promoting invasion of epicardium-derived cells into the myocardium by induction of extracellular matrix-degrading enzyme gene expression |
| protein
| c-Src and TRAF6 |
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cooperating with RANK (TNFRSF11A) prostaglandin receptor activator of NF kappa B |
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ZNF347 in osteoclastogenesis |
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ligand of osteoprotegerin |
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delta- CAPRI-Ras-MMP14 axis plays an important role in the TNFSF11 shedding |
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intreacting with CTSK and NFATC1 (valve leaflet morphogenesis involves NFATC1-dependent expression of remodeling enzymes including CTSK) |
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RAB27A and RAB27B are involved in the stimulation-dependent TNFSF11 release pathway in osteoblastic cells |
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TNFSF11 and TNFRSF11 interaction acts through MEK/ERK, which in turn activates NFKB, resulting in the activation of ICAM1 and contributing to the migration of human lung cancer cells |
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EGR2 is an important modulator of TNFSF11-induced osteoclast differentiation, providing the link between TNFSF11, EGR2 and ID proteins in osteoclast-lineage cells |
| induced by
| T cell activation |
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| E2F1 |
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| in vivo administration of medroxyprogesterone acetate triggers massive induction of the key osteoclast differentiation factor RANKL in mammary-gland epithelial cells |
|
| TNFSF11 (induces NFATC1 expression during osteoclastogenesis at a transcriptional level) |
| inhibited by
| TCR stimulation |
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| calcineurin-regulated transcription factors |
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| IL1B and TNFRSF11B |
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| IFNG through rapid degradation of TRAF6 |
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| multiple hormones and cytokines including vitamin D3,IL1,IL11,PGE2,CALCA,TNF |
| Other
| solubilized by MMP-7 |
| corresponding disease(s)
|
OPTB2
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| Other morbid association(s)
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| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
|
|---|
| constitutional
| germinal mutation
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associated with bone mineral density at different skeletal sites in adult men, but not in women | | constitutional
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|
| --over
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| |
in keratinocytes of the inflamed skin (resulted in functional alterations of epidermal dendritic cells and systemic increases of regulatory CD4(+)CD25(+) T cells) | | constitutional
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| --over
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significantly elevated in non-cirrhotic, chronic liver disease, which could modulate bone loss | | constitutional
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| --over
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in rheumatoid arthritis subchondral bone tissue biopsies | |
| Susceptibility
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to modification of Camurati-engelmann disease (CED) to Crohn disease |
| Variant & Polymorphism
other
| TNFSF11 variant associated with unique phenotype of CED |
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increasing the risk of Crohn disease |
| 
|
Candidate gene
Marker
Therapy target
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| System | Type | Disorder | Pubmed |
|---|
| allergy | | | |
| . local induction of TNFSF11/TNFRSF11A in the skin could be used as a therapeutic approach for allergies as well for systemic autoimmunity through increasing regulatory T cells
| | immunology | autoimmune | | |
| . local induction of TNFSF11/TNFRSF11A in the skin could be used as a therapeutic approach for allergies as well for systemic autoimmunity through increasing regulatory T cells
| | osteoarticular | bone | others | |
| . early TNFSF11 administration, as soluble RANKL treatment in mice, increases osteoclast number and stimulates bone resorption
| | cancer | metastases | | |
| . central role of TNFRSF11A/TNFSF11 pathway as potential therapeutic target not only in bone metastasis management, but also in the adjuvant setting |
| | | |
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| TRANCE-deficient mice showed severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibited profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae | |
mice lacking RANK fail to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns |
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RANKL overexpression in keratinocytes resulted in functional alterations of epidermal dendritic cells and systemic increases of regulatory CD4(+)CD25(+) T cells |
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Transgenic overexpression of TRANCE in lymphocytes of TRANCE-deficient mice rescued osteoclast development |
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deletion of RANK from the mammary epithelium results in a markedly decreased incidence and delayed onset of medroxyprogesterone acetate-driven mammary cancer |
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severe osteopetrotic phenotype observe in mice lacking RANKL specifically in osteocytes indicates that osteocytes are the major source of RANKL in bone remodeling |
