A novel mode of action for COX-2 inhibition: Targeting ATPase domain of HSP90 induces ubiquitin degradation of new client protein COX-2

  Cyclooxygenase 2 (COX-2) is the main target of nonsteroidal anti-inflammatory drugs (NSAIDs), and it is rapidly expressed in response to extracellular factor stimulation like lipopolysaccharide (LPS) in mouse monocyte macrophage 264.7 (RAW264.7) cells. Herein, we reveal the existence of a novel mechanism that intervenes the formation of the heat shock protein 90 (HSP90)/COX-2 complex and induces the ubiquitin-proteasomal degradation of COX-2.

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