A 59-kilodalton protein associated with progestin, estrogen, androgen, and glucocorticoid receptors

Tai, Ping; Maeda, Yoshiaki; Nakao, Kazuso; Wakim, Najib G.; Duhring, John L.; Faber, Lee E.

doi:10.1021/bi00366a043

Cited by 239 publications

(118 citation statements)

References 24 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…1 is a high molecular weight FK506-binding immunophilin first identified as a component of steroid hormone receptor heterocomplexes (1). Analysis of mRNA and protein levels has demonstrated that FKBP52 is widely expressed in mammalian tissues but particularly abundant in the nervous system (2, 3).…”

Section: Fkbp52mentioning

confidence: 99%

“…FKBP52 regulates the maturation of steroid hormone receptor complexes through interactions between its TPR domain and HSP90 chaperones, which act as scaffolds for receptor assembly and are thought to enhance the affinity of estrogen receptor and the glucocorticoid receptor toward their ligands (1,6). The PPIase domain of FKBP52 facilitates translocation of the activated steroid receptors to the nucleus by binding to cytoplasmic dynein (7).…”

Section: Fkbp52mentioning

confidence: 99%

See 1 more Smart Citation

A Novel Role for the Immunophilin FKBP52 in Copper Transport

Sanokawa-Akakura

Dai

Akakura

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

FK506-binding protein 52 (FKBP52) is an immunophilin that possesses peptidylprolyl cis/trans-isomerase(PPIase) activity and is a component of a subclass of steroid hormone receptor complexes. Several recent studies indicate that immunophilins can regulate neuronal survival and nerve regeneration although the molecular mechanisms are poorly understood. To investigate the function of FKBP52 in the nervous system, we employed a yeast two-hybrid strategy using the PPIase domain (domain I) as bait to screen a neonatal rat dorsal root ganglia cDNA expression library. We identified an interaction between FKBP52 domain I and Atox1, a copper-binding metallochaperone. Atox1 interacts with Menkes disease protein and Wilson disease protein (WD) and functions in copper efflux. The interaction between FKBP52 and Atox1 was observed in both glutathione S-transferase pull-down experiments and when proteins were ectopically expressed in human embryonic kidney (HEK) 293T cells and was sensitive to FK506. Interestingly, the FKBP52/Atox1 interaction was enhanced when HEK 293T cells were cultured in copper-supplemented medium and decreased in the presence of the copper chelator, bathocuproine disulfate, suggesting that the interaction is regulated in part by intracellular copper. Overexpression of FKBP52 increased rapid copper efflux in 64 Cu-loaded cells, as did the overexpression of WD transporter. Taken together, our present findings suggest that FKBP52 is a component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity. FKBP521 is a high molecular weight FK506-binding immunophilin first identified as a component of steroid hormone receptor heterocomplexes (1). Analysis of mRNA and protein levels has demonstrated that FKBP52 is widely expressed in mammalian tissues but particularly abundant in the nervous system (2, 3). Structurally, FKBP52 contains an N-terminal peptidylprolyl cis-trans-isomerase (PPIase) domain (domain I), a FKBP-like pseudo domain (domain II), three tetratricopeptide repeat (TPR) domains (domain III) that mediate proteinprotein interactions with HSP90, and a C-terminal domain calmodulin-binding site (domain IV) (4, 5).FKBP52 has been shown to play important roles in a diverse number of intracellular processes, but much research has focused on its involvement in steroid hormone regulation. FKBP52 regulates the maturation of steroid hormone receptor complexes through interactions between its TPR domain and HSP90 chaperones, which act as scaffolds for receptor assembly and are thought to enhance the affinity of estrogen receptor and the glucocorticoid receptor toward their ligands (1, 6). The PPIase domain of FKBP52 facilitates translocation of the activated steroid receptors to the nucleus by binding to cytoplasmic dynein (7). FKBP52 serves as a transcriptional regulator by repressing the activity of interferon regulatory factor-4 in immune cells (8) and heat-shock factor-1 in HeLa cells (9). FKBP52 has been implicated in the cardiotrophic effect of cardiotrophin-1 (10...

show abstract

Section: Fkbp52mentioning

confidence: 99%

Section: Fkbp52mentioning

confidence: 99%

A Novel Role for the Immunophilin FKBP52 in Copper Transport

Sanokawa-Akakura

Dai

Akakura

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The large immunophilin that was first identified to be a component of these complexes was FKBP52 (18,19). Sequence and hydrophobic cluster analysis suggested that FKBP52 is composed of four different domains (20).…”

Section: Conversion Of Prolyl Peptide Bonds From Trans-to Cis-prolinesmentioning

confidence: 99%

Localization of the Chaperone Domain of FKBP52

Pirkl¹,

Fischer²,

Modrow³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

FKBP52, a multidomain peptidyl prolyl cis/transisomerase (PPIase), is found in complex with the chaperone Hsp90 and the co-chaperone p23. It displays both PPIase and chaperone activity in vitro. To localize these two activities to specific regions of the protein, we created and analyzed a set of fragments of FKBP52. The PPIase activity toward both peptides and proteins is confined entirely to domain 1 (amino acids 1-148). The chaperone activity, however, resides in the C-terminal part of FKBP52, mainly in the region between amino acids 264 and 400 (domain 3). Interestingly, this domain also contains the tetratricopeptide repeats, which are responsible for the binding to C-terminal amino acids of Hsp90. Competition assays with a C-terminal Hsp90 peptide suggest that the non-native protein and Hsp90 are bound by different regions within this domain.

show abstract

“…The involvement of other molecular components is less clear. A polypeptide of Mr 59000 was detected in association with several steroid hormone receptors [13]. RNA has also been envisaged as part of large glucocorticoid receptors (review [14]).…”

Section: Introductionmentioning

confidence: 99%

Tetrameric structure of the nonactivated glucocorticoid receptor in cell extracts and intact cells

Rexin¹,

Busch²,

Segnitz³

et al. 1988

FEBS Letters

View full text Add to dashboard Cite

Mouse lymphoma cells contain a nonactivated glucocorticoid receptor of Mr ~ 330000 which is heteromeric in nature and is unable to bind to DNA. Following affinity labeling of the steroid-binding subunit and subsequent cross-linking with dimethyl suberimidate at various times either in cell extracts or in intact cells, a series of labeled bands was detected in SDS gels. From the molecular masses of completely and partially cross-linked complexes we conclude that the large nonactivated receptor is a tetramer composed of two 90 kDa subunits, one 50 kDa polypeptide and one steroid-binding subunit.

show abstract

A 59-kilodalton protein associated with progestin, estrogen, androgen, and glucocorticoid receptors

Cited by 239 publications

References 24 publications

A Novel Role for the Immunophilin FKBP52 in Copper Transport

A Novel Role for the Immunophilin FKBP52 in Copper Transport

Localization of the Chaperone Domain of FKBP52

Tetrameric structure of the nonactivated glucocorticoid receptor in cell extracts and intact cells

Contact Info

Product

Resources

About