Wnt/beta-catenin signaling: components, mechanisms, and diseases.
Signaling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator beta-catenin controls embryonic development and adult homeostasis. Here we review recent progress in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists, and antagonists, and their interactions with Wnt receptors. We also dissect critical events that regulate beta-catenin stability, from Wnt receptors to the cytoplasmic beta-catenin destruction complex, and nuclear machinery that mediates beta-catenin-dependent transcription. Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications.
MacDonald
Bryan T
BT
F. M. Kirby Neurobiology Center, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Tamai
Keiko
K
He
Xi
X
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D060466:Axin Protein; D004194:Disease; D051157:Frizzled Receptors / Q000378:metabolism; D006801:Humans; D008024:Ligands; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011973:Receptors, LDL / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D060466:Axin Protein; D051157:Frizzled Receptors; C555475:LRP6 protein, human; D008024:Ligands; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011973:Receptors, LDL; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin