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  Essential role of the unusual DNA-binding motif of BAG-1 for inhibition of the glucocorticoid receptor

Schmidt, U., Wochnik, G., Rosenhagen, M., Young, J., Hartl, F., Holsboer, F., et al. (2003). Essential role of the unusual DNA-binding motif of BAG-1 for inhibition of the glucocorticoid receptor. Journal of Biological Chemistry, 278(7), 4926-4931.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-9F37-4 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-9F38-2
Genre: Journal Article
Alternative Title : J. Biol. Chem.

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 Creators:
Schmidt, U, Author
Wochnik, GM, Author
Rosenhagen, MC, Author
Young, JC, Author
Hartl, FU, Author
Holsboer, F1, Author
Rein, T, Author
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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 Abstract: The co-chaperone BAG-1 is involved in the regulation of steroid hormone receptors, including the glucocorticoid receptor (GR). More recently, BAG-1 was found in the nucleus where it decreases GR transactivation. Moreover, nonspecific DNA binding of BAG-1 has been reported. We discovered that of the N- terminal part of BAG-1M, the first 8 amino acids are sufficient for DNA binding, containing a stretch of three lysines and a stretch of three arginines. Changing the spacing between these stretches had no effect on DNA binding. Surprisingly, this small, nonsequence-specific DNA binding domain was nonetheless necessary for the inhibitory function of BAG-1 for GR-dependent transcription, whereas the following serine- and threonine-rich E2X4 repeat domain was not. Mutational analysis of these two domains revealed that only mutants retaining DNA binding capability were able to down-regulate GR-mediated transactivation. Intriguingly, lack of DNA binding could not be functionally rescued by BAG-1M harboring a point mutation abolishing interaction with hsp70. Thus, DNA binding and hsp70 interaction are required in cis. We propose that the nonsequence-specific DNA-binding protein BAG-1 acts at specific chromosomal loci by interacting with other protein

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Language(s): eng - English
 Dates: 2003-02-14
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 3993
ISI: 000180968900076
 Degree: -

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Title: Journal of Biological Chemistry
  Alternative Title : J. Biol. Chem.
Source Genre: Journal
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Pages: - Volume / Issue: 278 (7) Sequence Number: - Start / End Page: 4926 - 4931 Identifier: ISSN: 0021-9258