AKT and Beta-Catenin Coordination
Epigenetic mechanisms have been proposed to play crucial roles in stem cell self-renewal and differentiation, but their precise functions remain largely unaddressed. Many transcription factors and chromatin remodeling proteins interact with nuclear β-catenin to mediate transcription and chromatin dynamics. We found nuclear β-catenin is activated by two key signaling pathways, PI3K/Akt and Wnt, and potentially promotes expansion of both HSCs and ISCs; however, the underlying mechanism needs to be characterized. Differentiation of mouse embryonic stem (ES) cells provides a good model to study the role of nuclear β-catenin. Recently, we found β-catenin plays crucial role in maintaining ground state stem cells by associating with a protein complex in mouse ES cells. Currently we are performing comprehensive transcriptional and epigenetic profiling to study the impact of protein complex associated with β-catenin on ES cell self-renewal.
A transcription regulator which
interacts with β-catenin,
retains on mitotic chromatin.
Images by Fang Tao.
Computational simulation modeling showing that doxorubicin docks at the site of β-catenin adjacent to the Ser552 residue that is known to be phosphorylated by Akt.