Inhibition of GR‐mediated transcription by p23 requires interaction with Hsp90

Abstract

p23 is a regulatory co‐chaperone of heat shock protein (Hsp) 90, but can also act as a general molecular chaperone by itself. Using novel point mutations of p23 that disrupt its interaction with Hsp90 we found its co‐chaperone function to be required for its inhibitory effect on glucocorticoid receptor (GR). The C‐terminal region of p23, which is required for its chaperone activity, is dispensable for inhibition of GR. Importantly, similar results were obtained with a constitutively active GR. Thus, the action of p23 on the nuclear stage of GR regulation requires its Hsp90 co‐chaperone function, but not its chaperone activity.