The Glomuvenous Malformation Protein Glomulin Binds Rbx1 and Regulates Cullin RING Ligase-Mediated Turnover of Fbw7

► Glmn binds the RING domain of Rbx1 and inhibits CRL1Fbw7 E3 ligase activity ► Glmn null mice phenotype partially mirrors that associated with loss of Fbw7 ► GVM Glmn mutants fail to bind Rbx1 leading to deregulation of Fbw7 stability ► GVM lesions reflect abnormal homeostasis of Fbw7, Cyclin E, and c-Myc