P300 Serine 89: A Critical Signaling Integrator and Its Effects on Intestinal Homeostasis and Repair.

ABSTRACT: Differential usage of Kat3 coactivators, CBP and p300, by β-catenin is a fundamental regulatory mechanism in stem cell maintenance and initiation of differentiation and repair. Based upon our earlier pharmacologic studies, p300 serine 89 (S89) is critical for controlling differential coactivator usage by β-catenin via post-translational phosphorylation in stem/progenitor populations, and appears to be a target for a number of kinase cascades. To further investigate mechanisms of signal integration effected by this domain, we generated p300 S89A knock-in mice. We show that S89A mice are extremely sensitive to intestinal insult resulting in colitis, which is known to significantly increase the risk of developing colorectal cancer. We demonstrate cell intrinsic differences, and microbiome com

SUBMITTER: Lai KKY 

PROVIDER: S-EPMC7999107 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature