Associative memory plays a role in ER-1α positive breast cancers

This perspective brings together multiple observations concerning the regulatory architecture and functional interactions of the TP53 gene and its isoforms. The TP53 gene encompasses an internal enhancer-promoter region (P2) located between exons 2 and 5, which is transactivated by full-length TAp53α, to drive the expression of truncated TP53 isoforms ΔN133p53α, β or γ. ΔN133p53α homo-monomers or dimers very likely form hetero-tetramers with homo-dimers of full-length TAp53α. The TAp53α-ΔN133p53 tetramer then acts as a transcription factor augmenting mitochondrial efficiency, DNA repair, telomere restoration and reversing cellular senescence, thus opposing many outputs of tumor suppressive TAp53α homo-tetramers. Other transcription factors, such as estrogen receptor (ER), OCT1, and SOX9 also may bind the P2 promoter-enhancer to promote transcription of oncogenic TP53 isoforms. These transcription factors, together with full-length TAp53α, appear to cooperate to maintain an open chromatin state in the P2 region in a manner reminiscent of a neural "associative memory" network.