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Description

Heat shock protein HSP 90-alpha (UniProt: P07900, also known as Heat shock 86 kDa, HSP 86, HSP86, Lipopolysaccharide-associated protein 2, LAP-2, LPS-associated protein 2, Renal carcinoma antigen NY-REN-38) is encoded by the HSP90AA1 (also known as HSP90A, HSPC1, HSPCA) gene (Gene ID: 3320) in human. HSP90 serves as a molecular chaperone that maintains the stability and functionality of numerous client proteins in an ATPase-dependent manner. It is known to interact dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle, and chaperone function. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. HSP90 and its co-chaperones are also shown to modulate transcription at least at three different levels (a) by altering the steady-state levels of certain transcription factors in response to various physiological cues (b) modulating the activity of certain epigenetic modifiers, such as histone deacetylases, and (c) by participation in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. In its resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer, which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. Following the completion of its chaperoning activity, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state. This monoclonal antibody (clone 1G6-D7) is reported to inhibit both de novo tumor formation and expansion of already formed tumors in mice. (Ref.: Li, W., et al. (2012). Biochim. Biophys. Acta. 1823(3), 730 741, Zou, M., et al. (2017). Oncogene 36(15), 2160-2171).