scholarly journals Noncatalytic Role of the FKBP52 Peptidyl-Prolyl Isomerase Domain in the Regulation of Steroid Hormone Signaling

2007 ◽  
Vol 27 (24) ◽  
pp. 8658-8669 ◽  
Author(s):  
Daniel L. Riggs ◽  
Marc B. Cox ◽  
Heather L. Tardif ◽  
Martin Hessling ◽  
Johannes Buchner ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Genetic Selection ◽  
Steroid Hormone Receptors ◽  
Hormone Signaling ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Isomerase Activity ◽  
Steroid Hormone Signaling

ABSTRACT Hormone-dependent transactivation by several of the steroid hormone receptors is potentiated by the Hsp90-associated cochaperone FKBP52, although not by the closely related FKBP51. Here we analyze the mechanisms of potentiation and the functional differences between FKBP51 and FKBP52. While both have peptidyl-prolyl isomerase activity, this is not required for potentiation, as mutations abolishing isomerase activity did not affect potentiation. Genetic selection in Saccharomyces cerevisiae for gain of potentiation activity in a library of randomly mutated FKBP51 genes identified a single residue at position 119 in the N-terminal FK1 domain as being a critical difference between these two proteins. In both the yeast model and mammalian cells, the FKBP51 mutation L119P, which is located in a hairpin loop overhanging the catalytic pocket and introduces the proline found in FKBP52, conferred significant potentiation activity, whereas the converse P119L mutation in FKBP52 decreased potentiation. A second residue in this loop, A116, also influences potentiation levels; in fact, the FKBP51-A116V L119P double mutant potentiated hormone signaling as well as wild-type FKBP52 did. These results suggest that the FK1 domain, and in particular the loop overhanging the catalytic pocket, is critically involved in receptor interactions and receptor activity.

scholarly journals Chaperoning steroid hormone signaling via reversible acetylation

2005 ◽  
Vol 3 (1) ◽  
pp. nrs.03004 ◽  
Author(s):  
Jeffrey J. Kovacs ◽  
Todd J. Cohen ◽  
Tso-Pang Yao
Keyword(s):  
Transcription Factors ◽  
Molecular Chaperone ◽  
Hormone Receptors ◽  
Binding Capacity ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Hormone Signaling ◽  
Protein Acetylation ◽  
Steroid Hormone Signaling ◽  
Chaperone Complex

Glucocorticoid receptor (GR) and related steroid hormone receptors are ligand-dependent transcription factors whose regulation is critical for both homeostasis and diseases. The structural maturation of the GR has been shown to require the Hsp90 molecular chaperone complex. Evidence indicates that Hsp90-dependent maturation is critical for GR ligand binding capacity and activity. While the role for Hsp90 in GR function is well established, the regulation of this process is not well understood. Here we discuss a recent finding that identifies reversible protein acetylation controlled by the deacetylase HDAC6 as a novel mechanism that regulates Hsp90-dependent GR maturation. We will also speculate on the implications of this finding in steroid hormone signaling, oncogenic transformation and its potential therapeutic utility.

scholarly journals Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation

1997 ◽  
Vol 328 (3) ◽  
pp. 807-813 ◽  
Author(s):  
Graham PACKHAM ◽  
Matthew BRIMMELL ◽  
L. John CLEVELAND
Keyword(s):  
Translation Initiation ◽  
Mammalian Cells ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Open Reading Frames ◽  
Steroid Hormone Receptors ◽  
Alternative Translation Initiation ◽  
Alternative Translation ◽  
Expression In Mammalian Cells ◽  
Reading Frames

The Bcl-2 oncoprotein is a key regulator of apoptosis and the Bag-1 protein interacts with Bcl-2 and cooperates with Bcl-2 to suppress apoptosis. The human Bag-1 cDNA is essentially identical with a previously described cDNA encoding RAP46, which interacts with activated steroid hormone receptors. However, there is considerable confusion over the structure of Bag-1/RAP46 proteins and their relationship to endogenous Bag-1 proteins. Here we have characterized Bag-1 expression in mammalian cells. We demonstrate that, in addition to the previously identified 32 kDa murine and 36 kDa human Bag-1 proteins, cells express a second 50 kDa Bag-1 isoform. In some murine cell lines p50 is expressed at the same level as p32 Bag-1, and p50 and p32 Bag-1 proteins have distinct subcellular localizations, suggesting that they are functionally distinct. The published mouse Bag-1 cDNA is partial, and sequencing of additional murine Bag-1 RNA 5ʹ sequences demonstrated that human and murine Bag-1 cDNAs contain longer open reading frames than originally suspected. We determined which open reading frames gave rise to the Bag-1 isoforms in human cells. Suprisingly, translation of neither protein initiated at the first in-frame methionine, and cells do not express Bag-1/RAP46 proteins with the previously proposed structures; p50 Bag-1 initiates at an upstream CUG codon, whereas p36 Bag-1 initiates at a downstream AUG codon. Therefore, cells express two differently localized Bag-1 isoforms generated by alternative translation initiation, and Bag-1 proteins may play a dual role in regulating apoptosis and steroid hormone-dependent transcription.

The Bovine Cervix During the Oestrous Cycle: Regional Differences in Morphology and Density of Steroid Hormone Receptors

2000 ◽  
Vol 35 (3-4) ◽  
pp. 120-124 ◽  
Author(s):  
VNA Breeveld-Dwarkasing ◽  
GC van der Weijden ◽  
MAM Taverne ◽  
FMF van Dissel-Emiliani
Keyword(s):  
Regional Differences ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Oestrous Cycle ◽  
Steroid Hormone Receptors

877 ROLE OF STEROID HORMONE RECEPTORS ON FORMATION AND PROGRESSION OF BLADDER CARCINOMA

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Gholamreza Pourmand ◽  
Sepehr Salem ◽  
Abdolrasoul Mehrsai ◽  
Farid Kosari
Keyword(s):  
Bladder Carcinoma ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors
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