The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor

@article{Shatkina2003TheCB,
  title={The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor},
  author={Liubov Shatkina and Sigrun Mink and Hermann Rogatsch and Helmut Klocker and Gernot Langer and Andrea Nestl and Andrew C B Cato},
  journal={Molecular and Cellular Biology},
  year={2003},
  volume={23},
  pages={7189 - 7197}
}
ABSTRACT Members of the Bag-1 family of cochaperones regulate diverse cellular processes including the action of steroid hormone receptors. The largest member of this family, Bag-1L, enhances the transactivation function of the androgen receptor. This occurs primarily through interaction with the NH2 and COOH termini of the receptor. At the NH2 terminus of the receptor, Bag-1L interacts with a region termed τ5. Bag-1M, a naturally occurring variant of Bag-1L that binds to τ5 but is defective in… Expand
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2
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References

SHOWING 1-10 OF 42 REFERENCES
BAG-1 family of cochaperones in the modulation of nuclear receptor action
  • A. Cato, S. Mink
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2001
TLDR
This review puts together recent findings on the action the BAG-1 proteins and presents them as a novel group of regulators of action of nuclear receptor. Expand
FXXLF and WXXLF Sequences Mediate the NH2-terminal Interaction with the Ligand Binding Domain of the Androgen Receptor*
TLDR
In a mammalian two-hybrid assay, glutathione S-transferase fusion protein binding studies, and functional assays that two predicted α-helical regions that are similar, but functionally distinct from the p160 coactivator interaction sequence, mediate the androgen-dependent, NH2- and carboxyl-terminal interaction are demonstrated. Expand
A Nuclear Action of the Eukaryotic Cochaperone Rap46 in Downregulation of Glucocorticoid Receptor Activity
TLDR
The studies identify the [EEX4]8 sequence as a signature motif for inhibition of GR-mediated transactivation and demonstrate a specific nuclear action of a eukaryotic cochaperone in the regulation of GR activity. Expand
BAG-1L Protein Enhances Androgen Receptor Function*
TLDR
BAG-1L significantly reduced the concentrations of 5α-dihydrotestosterone required for AR activity but did not induce ligand-independent transactivation, and markedly improved the ability of AR to transactivate reporter genes when cells were cultured with DHT in combination with the anti-androgen cyproterone acetate. Expand
Hsp70–RAP46 interaction in downregulation of DNA binding by glucocorticoid receptor
TLDR
Findings demonstrate an important contribution of Hsp70/Hsc70 in the binding of RAP 46 to the glucocorticoid receptor and suggest a role for this molecular chaperone in the RAP46‐mediated downregulation of glucoc Corticoid receptors activity. Expand
Activation Function 2 in the Human Androgen Receptor Ligand Binding Domain Mediates Interdomain Communication with the NH2-terminal Domain*
TLDR
Evidence is provided that activation function 2 in the androgen receptor serves as the contact site for theandrogen dependent NH2- and carboxyl-terminal interaction of the androgens receptor and only weakly interacts with p160 coactivators in an LXXLL-dependent manner. Expand
Structural analysis of BAG1 cochaperone and its interactions with Hsc70 heat shock protein
TLDR
A structure-based approach was used to identify interacting residues in a BAG1–Hsc70 complex and the results provide a structural basis for understanding the mechanism by which BAG proteins link molecular chaperones and cell signaling pathways. Expand
Evidence for an Anti-parallel Orientation of the Ligand-activated Human Androgen Receptor Dimer (*)
TLDR
The results indicate that high affinity androgen binding promotes interactions between the NH2-terminal and steroid-binding domains of human AR, raising the possibility of an androgen-induced anti-parallel AR dimer. Expand
N-terminal sequences of the human androgen receptor in DNA binding and transrepressing functions
TLDR
It appears that the structure rather than sequence specific elements determines the contribution of the N-terminus of the androgen receptor to DNA binding and transrepression functions. Expand
Identification of Two Transcription Activation Units in the N-terminal Domain of the Human Androgen Receptor (*)
TLDR
The data presented show that the size and location of the active TAU in the human AR is variable, being dependent on the promoter context and the presence or absence of the ligand binding domain. Expand
...
1
2
3
4
5
...