Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a ge...

INTRODUCTION: Bone remodeling, a dynamic process involving bone resorption followed by bone formation, takes place throughout life to maintain bone homeostasis. Osteoporosis pseudoglioma (OPPG) syndrome and high bone mass (HBM) syndrome are both mapped to the locus of Lrp5, a receptor for Wnt ligands in activation of β-catenin signaling (1). OPPG patients harbor inactivating mutations in the Lr...

Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest) and F2 (second largest) follicles isolated at predeviation ...

Background: In the absence of Wnt stimulation, the transcriptional cofactor b-catenin is destabilized via phosphorylation by protein kinase GSK3b in complex with Axin family members. In the ‘‘canonical’’ Wnt signaling pathway, Disheveled (Dvl) is required to functionally inhibit the activity of the GSK3b/Axin complex and thereby stabilize b-catenin. Yet, the mechanisms that underlie Wnt regulat...