Abstract:
BACKGROUND:The ancient and highly evolutionarily conserved Wnt signaling pathway is critical in nearly all tissues and organs for an organism to develop normally from embryo through adult. Wnt signaling is generally parsed into "canonical" or Wnt-β-catenin-dependent or "non-canonical" β-catenin-independent signaling. Even though designating Wnt signaling as either canonical or noncanonical allows for easier conceptual discourse about this signaling pathway, in fact canonical and non-canonical Wnt crosstalk regulates complex nonlinear networks. OBJECTIVE:In this perspective, we discuss the integration of canonical and non-canonical Wnt signaling via differential Kat3 (CBP and p300) coactivator usage, thereby regulating and coordinating gene expression programs associated with both proliferation and cellular differentiation and morphogenesis. METHODS:Pharmacologic inhibitors, cell culture, real-time PCR, chromatin immunoprecipitation, protein immunoprecipitation, Western blotting, reporter-luciferase, protein purification, site-directed mutagenesis, in vitro phosphorylation and binding assays, and immunofluorescence were utilized. CONCLUSION:Coordinated integration between both canonical and non-canonical Wnt pathways appears to be crucial not only in the control of fundamental morphologic processes but also in the regulation of normal as well as pathologic events. Such integration between both canonical and non-canonical Wnt signaling is presumably effected via reversible phosphorylation mechanism (e.g., protein kinase C) to regulate differential β -catenin/Kat3 coactivator usage in order to coordinate proliferation with differentiation and adhesion.
journal_name
Curr Mol Pharmacoljournal_title
Current molecular pharmacologyauthors
Lai KKY,Nguyen C,Lee KS,Lee A,Lin DP,Teo JL,Kahn Mdoi
10.2174/1874467212666190304121131subject
Has Abstractpub_date
2019-01-01 00:00:00pages
167-183issue
3eissn
1874-4672issn
1874-4702pii
CMP-EPUB-97022journal_volume
12pub_type
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journal_title:Current molecular pharmacology
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