FIG 9.

A model explaining the regulation of E2 protein stability in the presence of J2 fibroblasts. In the top panel E2 is complexed with TopBP1 and the ability of SIRT1 to deacetylate E2 is regulated, allowing a stable level of E2 expression. In the lower panel, if the E2 interaction with TopBP1 is disrupted (by E2 mutation, siRNA treatment of TopBP1, or the addition of CX4945 to disrupt the E2-TopBP1 interaction) then SIRT1 deacetylation of E2 is accelerated. This deacetylation promotes ubiquitination and subsequent proteasomal degradation of the E2 protein.