Author/Authors :
Sternsdorf، نويسنده , , Thomas and Phan، نويسنده , , Vernon T. and Maunakea، نويسنده , , Mei Lin and Ocampo، نويسنده , , Corinne B. and Sohal، نويسنده , , Jastinder and Silletto، نويسنده , , Angela and Galimi، نويسنده , , Francesco and Le Beau، نويسنده , , Michelle M. and Evans، نويسنده , , Ronald M. and Kogan، نويسنده , , Scott C.، نويسنده ,
Abstract :
Summary
ecomes an acute promyelocytic leukemia (APL) oncogene by fusion with any of five translocation partners. Unlike RARα, the fusion proteins homodimerize, which may be central to oncogenic activation. This model was tested by replacing PML with dimerization domains from p50NFκB (p50-RARα) or the rapamycin-sensitive dimerizing peptide of FKBP12 (F3-RARα). The X-RARα fusions recapitulated in vitro activities of PML-RARα. For F3-RARα, these properties were rapamycin sensitive. Although in vivo the artificial fusions alone are poor initiators of leukemia, p50-RARα readily cooperates with an activated mutant CDw131 to induce APL-like disease. These results demonstrate that the dimerization interface of RARα fusion partners is a critical element in APL pathogenesis while pointing to other features of PML for enhancing penetrance and progression.
