Figure 2. Lysine ε-amino deacetylation promotes protein turnover and shortens Foxp3 lifespan.

(1) HATs can acetylate lysine residues in Foxp3 at the ε-NH₂ group. In the acetylated form, the lysine residue cannot enter the ubiquitination reaction. (2) HDACs can remove the acetyl-group from Foxp3, and make it susceptible to the ubiquitination reaction. (3) Activated ubiquitin is formed by binding of its c-terminus to a cysteine residue on ubiquitin-activating enzyme (E1) via a thiol bond. Next, E1 is replaced by ubiquitin-conjugating enzyme (E2). (4) The E2-ubiquitin complex can be linked to deacetylated lysine residues on Foxp3 via an ubiquitin-protein ligase (E3) forming an isopeptide bond (5). (6) Subsequently, other ubiquitins can bind to the ε-amino groups of lysine residues (K29 and K48) of ubiquitin already bound to Foxp3. (7) A chain of four or more ubiquitins is sufficient to indicate proteins for degradation in the proteasome.