RANKL
RANKL, encoded by the TNFSF11 gene, is a member of the tumour necrosis factor family and a key osteoclast differentiation and activation factor. Also known as TRANCE, OPGL, ODF and CD254, it binds the receptor RANK and the decoy receptor osteoprotegerin. Browse Assay Genie's current range of RANKL research reagents below, or read on for the biology behind the target.
RANKL is a cytokine that binds to TNFRSF11A (RANK) and to TNFRSF11B (osteoprotegerin, OPG). It acts as an osteoclast differentiation and activation factor. In osteoclast precursor cells it activates several signalling pathways, chief among them long-lasting oscillations in intracellular Ca2+ concentration. These oscillations activate NFATC1, which moves to the nucleus and drives osteoclast-specific gene transcription. During differentiation, in a TMEM64- and ATP2A2-dependent manner, RANKL also induces activation of CREB1 and the mitochondrial reactive oxygen species generation needed for proper osteoclast formation.
Beyond bone, RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation and is considered a dendritic cell survival factor. It may regulate interactions between T cells and dendritic cells and contribute to the T-cell-dependent immune response. T cell activation has been reported to induce expression of the gene, leading to increased osteoclastogenesis and bone loss. RANKL may also contribute to enhanced bone resorption in humoral hypercalcaemia of malignancy. It has been shown to activate the antiapoptotic kinase AKT/PKB through a signalling complex involving SRC kinase and TRAF6, suggesting a role in regulating apoptosis.
The TNFSF11 gene is also listed as TRANCE, OPGL, ODF and CD254, and was previously named tumour necrosis factor (ligand) superfamily, member 11. The protein is found at the cell membrane, in the cytoplasm and in secreted form. Targeted disruption of the related gene in mice caused severe osteopetrosis and a lack of osteoclasts. These mice also showed defects in early T and B lymphocyte differentiation and failed to form lobulo-alveolar mammary structures during pregnancy.
RANKL is a central driver of osteoclast differentiation and activation, making it a core target for studying bone resorption and remodelling.
RANKL enhances dendritic cell stimulation of naive T cells and may regulate T-cell-dependent immune responses.
RANKL may contribute to enhanced bone resorption in humoral hypercalcaemia of malignancy, linking it to cancer research.
RANKL activates AKT/PKB through SRC and TRAF6, and drives Ca2+ oscillations and NFATC1 signalling in precursor cells.
RANKL is a TNF family cytokine that binds RANK and osteoprotegerin. It is an osteoclast differentiation and activation factor, inducing Ca2+ oscillations and NFATC1 activation in precursors. It also augments dendritic cell stimulation of naive T cells and helps regulate T-cell-dependent immune responses.
The gene symbol is TNFSF11, and RANKL is also known as TRANCE, OPGL, ODF and CD254. The UniProt name is tumour necrosis factor ligand superfamily member 11. Its previous HGNC name was tumour necrosis factor (ligand) superfamily, member 11.
Mouse and rat both carry a Tnfsf11 ortholog. Targeted disruption of the related gene in mice led to severe osteopetrosis, a lack of osteoclasts, defects in early T and B lymphocyte differentiation and failure of mammary lobulo-alveolar development. Check the datasheet of any product for its validated reactivity.
Other TNF superfamily ligands related to RANKL, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O14788; product specifications from Assay Genie datasheets.