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A specialized Hsp90 co-chaperone network regulates steroid hormone receptor response to ligand

ABSTRACT: Heat shock protein-90 chaperone machinery is involved in the stability and activity of its client proteins. The chaperone function of Hsp90 is regulated by co-chaperones and post-translational modifications. Although structural evidence exists for Hsp90 interaction with clients, our understanding of the impact of Hsp90 chaperone function towards client activity in cells remains elusive. Here, we dissected the impact of newly identified co-chaperones in higher eukaryotes, FNIP1/2 (FNIPs) and Tsc1, towards Hsp90 client activity. Our data show that Tsc1 and FNIP2 form mutually exclusive complexes with FNIP1 and that unlike Tsc1, FNIP1/2 interact with the catalytic residue of Hsp90. Functionally, these co-chaperone complexes increase the affinity of the steroid hormone receptors glucocorticoid receptor and estrogen receptor to their ligands in vivo. Here, we provide a model for the responsiveness of the steroid hormone receptor activation upon ligand binding as a consequence of their association with specific Hsp90:co-chaperone subpopulations.

INSTRUMENT(S): 5800 TOF/TOF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast, Kidney

DISEASE(S): Tuberous Sclerosis,Kidney Cancer

SUBMITTER: Sarah Backe

LAB HEAD: Mehdi Mollapour

PROVIDER: PXD030486 | Pride | 2023-05-30

REPOSITORIES: Pride

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			Action	DRS
	PRIDE-SEARCH.xlsx	Xlsx
	checksum.txt	Txt
	lz_170512_EDJ67_FN.raw	Raw
	lz_170512_EDJ67_T.raw	Raw
	mz_220219_MM1025_20pct_EV_A.raw	Raw

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