| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T56510 | ||||
| Target Name | Antiapoptotic protein BCL-XL | ||||
| Target Type | Clinical Trial |
||||
| Drug Potency against Target | ABT-263 | Drug Info | Ki < 0.5 nM | [552892] | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | To investigate the role of Bcl-xL in osteoclasts, we generated mice with osteoclast-specific conditional deletion of Bcl-x (referred to herein as Bcl-x cKO mice) by mating Bcl-xfl/fl mice with mice in which the gene encoding the Cre recombinase has been knocked into the cathepsin K locus and specifically expressed in mature osteoclasts. Although the Bcl-x cKO mice grew normally with no apparent morphological abnormalities, they developed substantial osteopenia at 1 year of age, which was caused by increased bone resorption. Bcl-x deficiency increased the bone-resorbing activity of osteoclasts despite their high susceptibility to apoptosis, whereas Bcl-xL overexpression produced the opposite effect. In addition, Bcl-x cKO osteoclasts displayed increased c-Src activity, which was linked to increased levels of vitronectin and fibronectin expression. These results suggest that Bcl-xL attenuates osteoclastic bone-resorbing activity through the decreased production of ECM proteins, such as vitronectin and fibronectin, and thus provide evidence for what we believe to be a novel cellular function of Bcl-xL | [552892] | |||
| References | |||||
| Ref 552892 | BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):989-1000. doi: 10.1038/nrd2658. | ||||
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