Inhibition of GR-mediated transcription by p23 requires interaction with Hsp90.
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.
Max Planck Institute of Psychiatry, Kraepelinstrasse 10, D-80804 Munich, Germany.
Gabriela M
GM
Wochnik
Jason C
JC
Young
Ulrike
U
Schmidt
Florian
F
Holsboer
F Ulrich
FU
Hartl
Theo
T
Rein
D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins; D009447:Neuroblastoma; D017354:Point Mutation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D008164:Luminescent Proteins; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; C073446:protein p23; D049452:Green Fluorescent Proteins; D008156:Luciferases