of the HSP90AA1 gene is currently understood to be induced by stress through binding of the master transcription factor (TF) HSF1 to the HSP90AA1 promoter However, several focused studies of the HSP90AA1 promoter along with extensive global analysis of the human genome indicate that various other transcription complexes regulate HSP90AA1 gene expression. Mammalian HSP90AA1 along with HSP90AB1 gene expression was first characterized in transformed mouse cells where it was shown that HSP90AB1 is constitutively expressed 2.5-fold higher than HSP90AA1 under normal conditions. However upon heat shock, HSP90AA1 expression increased 7.0-fold while HSP90AB1 increases only 4.5-fold. Detailed analysis of the HSP90AA1 promoter shows that there are 2 heat shock elements (HSE) within 1200 bp of the transcription start site. The distal HSE is required for heat shock induction and the proximal HSE functions as a permissive enhancer. This model is supported by ChIP-SEQ analysis of cells under normal conditions where HSF1 is found bound to the proximal HSE and not detected at the distal HSE. The proto-oncogene MYC is also found to induce HSP90AA1 gene expression and binds proximally to the TSS as verified by ChIP-SEQ. Depletion of Hsp90A expression indicates that HSP90AA1 is required for MYC-driven transformation. In breast cancer cells the growth hormone prolactin induces HSP90AA1 expression through STAT5. NF-κB or RELA also induces HSP90AA1 expression possibly explaining the pro-survival ability of NF-κB-driven transcription. Conversely, STAT1, the proto-tumor suppressor, is found to inhibit stress induced expression of HSP90AA1. In addition to these findings, ChIP-SEQ analysis of the human genome indicates that at least 85 unique TFs bind to the RNA polymerase II (POLR2A) footprints associated with the promoter regions that drive the expression of both HSP90AA1 transcript variants. This indicates that HSP90AA1 gene expression may be highly regulated and complex. Interactome Combined, Hsp90A and Hsp90B are predicted to interact with 10% of the eukaryotic proteome. In humans this represents a network of roughly 2,000 interacting proteins. Presently over 725 interactions have been experimentally documented for both HSP90A and Hsp90B. This connectivity allows Hsp90 to function as a network hub linking diverse protein interaction networks. Within these networks Hsp90 primarily specializes in maintaining and regulating proteins involved in signal transduction or information processing. These include transcription factors that initiate gene expression, kinases that transmit information by post-translationally modifying other proteins and E3-ligases that target proteins for degradation via the proteosome. Indeed, a recent study utilizing the LUMIER method has shown