Nucleic Acids Research Advance Access originally published online on August 28, 2007
Nucleic Acids Research 2007 35(17):5954-5965; doi:10.1093/nar/gkm642
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Nucleic Acids Research, 2007, Vol. 35, No. 17 5954-5965
© 2007 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.
Molecular Biology |
The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP
1UMR 1019 of Human Nutrition and 2Proteomic core facility, INRA de Theix, 63122 Saint Genès Champanelle, France
*To whom correspondence should be addressed. Tel: +33 4 73 62 41 50; Fax: +33 4 73 62 47 55; Email: bruhat{at}clermont.inra.fr
Correspondence may also be addressed to Pierre Fafournoux. Tel: +33 4 73 62 45 62; Fax: +33 4 73 62 47 55; Email: fpierre{at}clermont.inra.fr
Received May 30, 2007. Revised August 2, 2007. Accepted August 3, 2007.
When an essential amino acid is limited, a signaling cascade is triggered that leads to increased translation of the ‘master regulator’, activating transcription factor 4 (ATF4), and resulting in the induction of specific target genes. Binding of ATF4 to the amino acid response element (AARE) is an essential step in the transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation. We set out to identify proteins that interact with ATF4 and that play a role in the transcriptional activation of CHOP. Using a tandem affinity purification (TAP) tag approach, we identified p300/CBP-associated factor (PCAF) as a novel interaction partner of ATF4 in leucine-starved cells. We show that the N-terminal region of ATF4 is required for a direct interaction with PCAF and demonstrate that PCAF is involved in the full transcriptional response of CHOP by amino acid starvation. Chromatin immunoprecipitation analysis revealed that PCAF is engaged on the CHOP AARE in response to amino acid starvation and that ATF4 is essential for its recruitment. We also show that PCAF stimulates ATF4-driven transcription via its histone acetyltransferase domain. Thus PCAF acts as a coactivator of ATF4 and is involved in the enhancement of CHOP transcription following amino acid starvation.
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