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A specific corepressor/coactivator e...
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Perissi, Valentina.
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A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors.
Record Type:
Electronic resources : Monograph/item
Title/Author:
A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors./
Author:
Perissi, Valentina.
Description:
107 p.
Notes:
Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0168.
Contained By:
Dissertation Abstracts International65-01B.
Subject:
Health Sciences, Pathology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120447
ISBN:
0496678132
A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors.
Perissi, Valentina.
A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors.
- 107 p.
Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0168.
Thesis (Ph.D.)--University of California, San Diego, 2004.
The mechanisms that control the precisely regulated switch from gene repression to gene activation represent a central question in mammalian development. Nuclear receptors represent a class of transcription factors, whose modulation by ligand binding is fundamental for cell growth and cell differentiation, for development and homeostasis.
ISBN: 0496678132Subjects--Topical Terms:
1017854
Health Sciences, Pathology.
A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors.
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A specific corepressor/coactivator exchange complex required in development and homeostasis for transcriptional activation by nuclear receptors, and other transcription factors.
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107 p.
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Source: Dissertation Abstracts International, Volume: 65-01, Section: B, page: 0168.
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Chair: Michael G. Rosenfeld.
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Thesis (Ph.D.)--University of California, San Diego, 2004.
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The mechanisms that control the precisely regulated switch from gene repression to gene activation represent a central question in mammalian development. Nuclear receptors represent a class of transcription factors, whose modulation by ligand binding is fundamental for cell growth and cell differentiation, for development and homeostasis.
520
$a
In the first Chapter of this dissertation I report the characterization of the interaction of the corepressors N-CoR/SMRT with the unliganded nuclear receptors. The NCoR and SMRT nuclear receptor interaction motifs exhibit a consensus sequence of LXX I/H I XXX I/L, representing an extended helix compared to the coactivator LXXLL helix, which is able to interact with specific residues in the same receptor pocket required for coactivator binding. Thus, the exchange between co-repressors and co-activators depends on the difference in the length of their alpha-helices and the preferential binding of either one by the receptor depends on the position of its C-terminal activation helix (AF2), whose movement is directly regulated by ligand binding.
520
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In the following Chapters, instead, I approach the same problem from a different angle and describe an additional level of regulation for the exchange of corepressors for coactivators. Transcriptional activation mediated by liganded nuclear receptors unexpectedly requires the actions of two highly related F-box/WD-40 containing factors, TBL1 and TBLR1, initially identified as components of an N-CoR corepressor complex. I propose that TBL1/TBLR1 serve as specific adaptors for the recruitment of the ubiquitin conjugating/19S proteasome complex, with TBLR1 selectively serving to mediate a required exchange of the nuclear receptor corepressors, N-CoR and SMRT, for coactivators upon ligand binding. The role of TBLR1 and TBL1 in cofactor exchange appears to also operate for c Jun and NFkappaB, and is therefore likely to be prototypic of similar mechanisms for other signal-dependent transcription factors.
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School code: 0033.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3120447
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