English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  The Mode of Stem Cell Division Is Dependent on the Differential Interaction of β-Catenin with the Kat3 Coactivators CBP or p300.

Lukaszewicz, A. I., Nguyen, C., Melendez, E., Lin, D. P., Teo, J.-L., Lai, K. K. Y., et al. (2019). The Mode of Stem Cell Division Is Dependent on the Differential Interaction of β-Catenin with the Kat3 Coactivators CBP or p300. Cancers, 11(7): E962. doi:10.3390/cancers11070962.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Lukaszewicz, Agnes I, Author
Nguyen, Cu, Author
Melendez, Elizabeth, Author
Lin, David P, Author
Teo, Jia-Ling, Author
Lai, Keane K Y, Author
Huttner, Wieland1, Author           
Shi, Song-Hai, Author
Kahn, Michael, Author
Affiliations:
1Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

Content

show
hide
Free keywords: -
 Abstract: Normal long-term repopulating somatic stem cells (SSCs) preferentially divide asymmetrically, with one daughter cell remaining in the niche and the other going on to be a transient amplifying cell required for generating new tissue in homeostatic maintenance and repair processes, whereas cancer stem cells (CSCs) favor symmetric divisions. We have previously proposed that differential β-catenin modulation of transcriptional activity via selective interaction with either the Kat3 coactivator CBP or its closely related paralog p300, regulates symmetric versus asymmetric division in SSCs and CSCs. We have previously demonstrated that SSCs that divide asymmetrically per force retain one of the dividing daughter cells in the stem cell niche, even when treated with specific CBP/β-catenin antagonists, whereas CSCs can be removed from their niche via forced stochastic symmetric differentiative divisions. We now demonstrate that loss of p73 in early corticogenesis biases β-catenin Kat3 coactivator usage and enhances β-catenin/CBP transcription at the expense of β-catenin/p300 transcription. Biased β-catenin coactivator usage has dramatic consequences on the mode of division of neural stem cells (NSCs), but not neurogenic progenitors. The observed increase in symmetric divisions due to enhanced β-catenin/CBP interaction and transcription leads to an immediate increase in NSC symmetric differentiative divisions. Moreover, we demonstrate for the first time that the complex phenotype caused by the loss of p73 can be rescued in utero by treatment with the small-molecule-specific CBP/β-catenin antagonist ICG-001. Taken together, our results demonstrate the causal relationship between the choice of β-catenin Kat3 coactivator and the mode of stem cell division.

Details

show
hide
Language(s):
 Dates: 2019-07-09
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3390/cancers11070962
Other: cbg-7461
PMID: 31324005
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cancers
  Other : Cancers (Basel)
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 11 (7) Sequence Number: E962 Start / End Page: - Identifier: -