**3.1 Transcriptional regulation of AIB1**

AIB1 protein level is regulated by multiple processes, with levels primarily peaking during the cell cycle. AIB1 autoregulates its own expression and is recruited to its own promoter in complex with E2F1 (see Section 6.3). AIB1 transcription is responsive to cell cycle cues mediated by Rb hypophosphorylation and resulting activation of E2F; thus, AIB1 levels increase during G1, and attenuate during S phase (when comparing relative levels during the cell cycle) [29]. Downregulation of AIB1 protein levels is, in part, mediated by the FoxG1 tumor suppressor, which acts by interacting with AIB1 and disrupting the interaction with E2F1 on its own promoter (FoxG1 additionally interrupts AIB1's activity with other transcription factors, such as NFκB, AP-1, and the Estrogen Receptor) [30]. Tight control of the AIB1 activity is regulated by its own positive feedback and tempered by inhibitory protein interactions.

AIB1 is also targeted by microRNA that regulates its expression. miR-17-5p targets at least two sites on the AIB1 mRNA, and miR-20b also binds to AIB1 mRNA. The two miRs are negatively correlated with AIB1 expression and loss of miR expression is associated with taxol resistance in breast cancer [31, 32]. These miRs, in addition to down regulating AIB1, interact with multiple other proteins to differentially regulate their gene expression. As a result, they are implicated in the progression or suppression of several cancers, in a context dependent manner.
