**3.3 AIB1 post-translational modifications modulate activity**

AIB1 is phosphorylated at different serine and threonine residues throughout the different domain structures by a variety of kinases. As a result, AIB1 is responsive to many different upstream signaling cascades, contributing to its oncogenic nature. JNK, p38, ERK, IKK, and PKA can all phosphorylate AIB1 at different residues to promote interaction with CBP and subsequently activate transcription (see **Figure 1**). Phosphorylation sites within AIB1 have been well profiled as mediators of certain protein-protein interactions. Six phosphorylation sites were originally described as essential for interaction with the estrogen and androgen receptors (T24, S505, S543, S857, S860, and S867). Conversely, phosphorylation at only T24 and S867 was required for TNF mediated NFκB interaction and activity [35]. These phosphorylation events in response to estradiol, TNFα, and upstream IGF signaling thus activate AIB1 to interact with partners and potentiate transcription [35–37]. Additionally, we have found that Abl kinase phosphorylates AIB1 at Y1357 in response to IGF, EGF and estradiol stimulation, which results in AIB1 interaction with essential chromatin modifying enzymes. This phosphorylation event is critical for AIB1's coactivator function [38]. Phosphorylation of AIB1 is thus a critical step in activation of the protein and is mediated by a variety of upstream signals that converge on the oncogenic coactivator. Some phosphorylation sites are required for all described activity, yet much work needs to be done to better understand what regulates the selectivity of AIB1 to bind with specific transcription factors and nuclear receptors.
