RNA levels measured in cell lines collected from cancer patients as well as normal tissue can be found at The Human Protein Atlas.

[8] 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.

[9] Detailed analysis of the HSP90AA1 promoter shows that there are 2 heat shock elements (HSE) within 1200 bp of the transcription start site.

[15] 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.

Within these networks Hsp90 primarily specializes in maintaining and regulating proteins involved in signal transduction or information processing.

Indeed, a recent study utilizing the LUMIER method has shown that human Hsp90B interacts with 7% of all transcription factors, 60% of all kinases and 30% of all E3-ligases.

[33] Gene ontology analysis of both Hsp90A and Hsp90B interactomes indicate that each paralogs is associated with unique biological processes, molecular functions and cellular components.

Heat shock protein 90kDa alpha (cytosolic), member A1 has been shown to interact with: Post-translational modifications have a large impact on Hsp90 regulation.

These unique phosphorylation sites signal Hsp90A for functions such as secretion, allow it to locate to regions of DNA damage and interact with specific co-chaperones.

Increased levels of Hsp90A are found in leukemia, breast and pancreatic cancers as well as in patients with chronic obstructive pulmonary disease (COPD).

HSP90 interacts and supports numerous proteins that promote oncogenesis, thus distinguishing Hsp90 as a cancer enabler as it is regarded as essential for malignant transformation and progression.

Additionally, whole genome sequencing across all tumor types and cancer cell lines reveals that there are presently 115 different mutations within the HSP90AA1 open reading frame.

This is supported by a comparative genome-wide analysis of 206 gastric cancer patients that reported loss of HSP90AA1 is indeed associated with favorable outcomes after surgery alone.

[96][97] Biologically, Hsp90A differs from Hsp90B in that Hsp90A is presently understood to function as a secreted extracellular agent in wound healing and inflammation in addition to its intracellular roles.

[98] Current research in prostate cancer indicates that extracellular Hsp90A transduces signals that promote the chronic inflammation of cancer-associated fibroblasts.

This reprogramming of the extracellular milieu surrounding malignant adenocarcinoma cells is understood to stimulate prostate cancer progression.

This concept requires further attention as it may explain the correlation of increased levels of Hsp90A in the plasma of patients with advanced stages of malignancy.

Hsp90 inhibitors interfere with this cycle at its early stages by replacing ATP, leading to the regulated ubiquitination and proteasome-mediated degradation of most client proteins.

Although many of the afore-mentioned inhibitors share the same Hsp90 binding site (either N- or C-terminal), it has been shown that some of these drugs preferentially access distinct Hsp90 populations, which are differentiated by the extent of their post-translational modification.