title: [Implication of the ubiquitin ligase c-Cbl in bone formation and tumorigenesis].
abstract: Cbl ubiquitin ligases are important molecules that control the process of ubiquitination and degradation of proteins by the proteasome. Because this process regulates several intracellular mechanisms, alterations in Cbl activity lead to several pathologies including cancer. In bone, the c-Cbl ubiquitin ligase is known to control osteoclast activity. Our studies indicate that c-Cbl also regulates osteoblast proliferation, differentiation and survival. We recently showed that inhibition of c-Cbl activity using a c-Cbl mutant leads to promote osteoblast differentiation in mesenchymal stromal cells as a consequence of increased receptor tyrosine kinase expression. Conversely, we found that overexpression of c-Cbl leads to inhibit osteosarcoma cell proliferation and tumorigenesis through downregulation of these receptors. Thus, the use of pharmacological agents capable of modulating c-Cbl activity may be of therapeutic interest for promoting bone formation in normal bone, or to reduce tumorigenesis in primary bone cancer.
authors.affiliation: Université Paris-Diderot Sorbonne Paris-Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sévère
authors.forename: Pierre
authors.initials: P
authors.lastname: Marie
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D001862:Bone Resorption / Q000201:enzymology*; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D010006:Osteoblasts / Q000201:enzymology*; D010010:Osteoclasts / Q000201:enzymology*; D010012:Osteogenesis / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D050721:Proto-Oncogene Proteins c-cbl / Q000037:antagonists & inhibitors / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D054875:Ubiquitination
chemical_list: D009363:Neoplasm Proteins; D050721:Proto-Oncogene Proteins c-cbl; D020794:Receptor Protein-Tyrosine Kinases; D046988:Proteasome Endopeptidase Complex