The AIB1/NCOA3/SRC-3 Oncogene

A member of the NCOA/SRC/p160 co-activator family, AIB1 is amplified and overexpressed in multiple cancer types, notably breast, ovarian, and pancreatic cancer. Common to all members of the NCOA/SRC/p160 family are bHLH-PAS, receptor interaction, and CBP/p300 interacting activation domains. The protein acts as a scaffold to support the transcriptional activity of many DNA binding transcription factors, such as the ER, AP-1, E2F, NF κ B, and TEADs. In doing so, the multi-domain protein facilitates chromatin remodeling and oncogenic gene transcription. Further, the AIB1Δ4 isoform promotes tumorigenesis and metastasis through interaction with chromatin in the nucleus or at the periphery of the cell. Pathologically, AIB1 promotes the transformation of normal tissue to cancerous lesions in multiple diseases, and loss delays progression. AIB1 has also been implicated in cancer recurrence and pharmacological resistance. We will discuss the structure and isoforms of AIB1, the physiological consequences of its interaction with transcription factors and hormone receptors, and clinical significance of the protein.