**Figure 2.**

*Oncogenic effects and gene expression changes involving direct AIB1 interaction with transcription factors and membrane proteins. Graphical depiction of AIB1 interaction with binding partners, resulting phenotypic behavior, and select transcriptional targets (italicized).*

transformation of normal tissue and the progression of disease. The effectors bind with the TEAD family of proteins to exert their oncogenic potential as a transcription factor complex [56–58]. Before paralogs YAP and TAZ, were implicated as transactivators of the TEAD family of transcription factors, the TEAD family was shown to interact with all the members of Nuclear Coactivator Family [8]. Specifically, the bHLH-PAS domain of AIB1 interacts with TEADs, likely in a larger complex with YAP or TAZ, and may then recruit histone modifying proteins to propagate transcription as measured by target genes [59]. Similarly, knockdown of AIB1 in cell lines significantly reduces TEAD target genes CTGF and CYR61 [60]. Currently, it is unclear to what extent the oncogenic YAP/TAZ-TEAD complex requires AIB1 or other members of the NCOA family to act as oncogenes. Knockdown of AIB1 in multiple studies has resulted in a modest, but significant reduction of TEAD transcriptional targets [60]. Interestingly, the Drosophila homolog of AIB1, called Taiman, contains PPxY motifs that are known to interact with the YAP homolog at its conserved WW domain. These PPxY motifs, however, are neither conserved in human AIB1, nor any member of the NCOA/SRC/p160 family [61].

Importantly, AIB1 may be the critical mediator of TEAD cooperation with AP-1. Early reports show an oncogenic signature associated with AP-1 and TEAD co-occupancy in triple negative breast cancer that promotes more aggressive disease [62]; this interaction was recently show to be mediated by AIB1 acting as a bridge between AP-1 and TEAD [59]. However, a clear panel of genes co-regulated by AIB1-TEAD interaction has yet to be elucidated. Further, while reports have shown AIB1 to be part of the TEAD-SRF (Serum Response Factor) complex, the data is unclear as to whether AIB1 is required for complex formation, or whether YAP can recruit SRF in the absence of AIB1 [60, 63]. It is apparent that TEAD, AP-1, and SRF all have coordinated responses to external growth stimuli [64], but the extent to which AIB1 and other co-activators are required to propagate and potentiate oncogenic signaling remains an exciting and unanswered question.
