p160/SRC/NCoA coactivators form complexes via specific interaction of their PAS-B domain with the CID/AD1 domain
- Transcriptional activation involves the ordered recruitment of coactivators via direct interactions between distinct binding domains and recognition motifs. The p160/SRC/NCoA coactivator family comprises three members (NCoA-1, -2 and -3), which are organized in multiprotein coactivator complexes. We had identified the PAS-B domain of NCoA-1 as an LXXLL motif binding domain. Here we show that NCoA family members are able to interact with other full-length NCoA proteins via their PAS-B domain and they specifically interact with the CBP-interaction domain (CID/AD1) of NCoA-1. Peptide competition, binding experiments and mutagenesis of LXXLL motifs point at distinct binding motif specificities of the NCoA PAS-B domains. NMR studies of different NCoA-1-PAS-B/LXXLL peptide complexes revealed similar although not identical binding sites for the CID/AD1 and STAT6 transactivation domain LXXLL motifs. In mechanistic studies, we found that overexpression of the PAS-B domain is able to disturb the binding of NCoA-1 to CBP in cells and that a CID/AD1 peptide competes with STAT6 for NCoA-1 in vitro. Moreover, the expression of an endogenous androgen receptor target gene is affected by the overexpression of the NCoA-1 or NCoA-3 PAS-B domains. Our study discloses a new, complementary mechanism for the current model of coactivator recruitment to target gene promoters.
Author: | Marco Lodrini, Tobias Münz, Nicolas Coudevylle, Christian GriesingerORCiDGND, Stefan Becker, Edith PfitznerORCiDGND |
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URN: | urn:nbn:de:hebis:30-57982 |
DOI: | https://doi.org/10.1093/nar/gkn029 |
ISSN: | 1362-4962 |
ISSN: | 0305-1048 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/18267973 |
Parent Title (English): | Nucleic acids research |
Publisher: | Oxford Univ. Press |
Place of publication: | Oxford |
Document Type: | Article |
Language: | English |
Year of Completion: | 2008 |
Date of first Publication: | 2008/04/01 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2008/10/02 |
Tag: | Molecular biology |
Volume: | 36 |
Issue: | 6 |
Page Number: | 15 |
First Page: | 1847 |
Last Page: | 1860 |
Note: | © 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Source: | Nucleic Acids Research 2008 36(6):1847-1860; doi:10.1093/nar/gkn029 |
HeBIS-PPN: | 206043546 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Sammlung Biologie / Sondersammelgebiets-Volltexte |
Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell 2.0 |