Ubiquitylation in Differentiation/Stem Cell

Cellular proliferation and differentiation are highly coordinated during development. In principle, cell differentiation requires several critical cellular processes including cell cycle arrest, initiation of differentiation program, and maintenance of differentiated status. The ubiquitin-proteasome system is thought to be as the key machinery orchestrating the above steps through regulating activators or inhibitors of cell cycle progression. In addition, ubiquitin-dependent proteolysis is suggested to be involved in modulating stem cell self-renewal or differentiation via regulation of signal transduction. Evidence based on develop-mental studies implicates the role of Cdh1-APC in various type of cellular differentiation. To elucidate the mechanism by which Cdh1-APC governs cellular differentiation, we are integrating RNA interference and protein purification approaches to analyze Cdh1-APC function and further identify its targets during cellular differentiation in a cultured cell based induction and mouse systems.