Convergence of Canonical and Non-Canonical Wnt Signal : Differential Kat3 Coactivator Usage

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Current molecular pharmacology - 12(2019), 3 vom: 29., Seite 167-183

Sprache:

Englisch

Beteiligte Personen:

Lai, Keane K Y [VerfasserIn]
Nguyen, Cu [VerfasserIn]
Lee, Kyung-Soon [VerfasserIn]
Lee, Albert [VerfasserIn]
Lin, David P [VerfasserIn]
Teo, Jia-Ling [VerfasserIn]
Kahn, Michael [VerfasserIn]

Links:

Volltext

Themen:

CBP
CREB-Binding Protein
CREBBP protein, human
Canonical
E1A-Associated p300 Protein
EC 2.3.1.48
EP300 protein, human
Journal Article
Kat3 coactivator
Non-canonical
P300.
Research Support, N.I.H., Extramural
Wnt

Anmerkungen:

Date Completed 26.03.2020

Date Revised 14.01.2021

published: Print

Citation Status MEDLINE

doi:

10.2174/1874467212666190304121131

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM294610278