Article Information
PubMed
Related Articles
- Ordered RecruitmentOrdered Recruitment
Molecular Cell, Volume 10, Issue 2, 1 August 2002, Pages 227-236
Maria Pia Cosma
SummaryActivators, chromatin-modifying enzymes, and basal transcription factors unite to activate genes, but are recruited in a precise order to promoters. The timing of the activation of transcription and the ordered recruitment of factors to promoters are the engines which, at the right moment and for the right length of time, drive the transcriptional regulation of each gene throughout the life of a cell.
Summary | Full Text | PDF (334 kb) - Regulation of FoxO activity by CBP/p300-mediated acetylation...Regulation of FoxO activity by CBP/p300-mediated acetylation
Trends in Biochemical Sciences, Volume 30, Issue 2, 1 February 2005, Pages 81-86
Lars P. van der Heide and Marten P. Smidt
AbstractForkhead box, class O (FoxO) transcription factors are inhibited by insulin-induced FoxO phosphorylation. Recently, acetylation of FoxO factors by calcium response element-binding (CREB)-binding protein (CBP) and/or p300 has been identified as a novel regulatory pathway, although the exact consequences of acetylation remain unclear. We propose that binding of CBP/p300 to FoxO factors is essential for FoxO-mediated transcription. CBP and p300 act as FoxO cofactors by weakening histone–DNA interactions. Acetylation of FoxO factors, however, attenuates FoxO-mediated transcriptional activity by disrupting the interaction between FoxO factors and target DNA. Therefore, acetylation shifts the function of FoxO from cell-cycle arrest and protection against oxidative stress towards cell death.
Abstract | Full Text | PDF (136 kb) - Control of Smad7 Stability by Competition between Acetylatio...Control of Smad7 Stability by Competition between Acetylation and Ubiquitination
Molecular Cell, Volume 10, Issue 3, 1 September 2002, Pages 483-493
Eva Grönroos, Ulf Hellman, Carl-Henrik Heldin and Johan Ericsson
SummarySmad proteins regulate gene expression in response to TGFβ signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus. Acetylation or mutation of these lysine residues stabilizes Smad7 and protects it from TGFβ-induced degradation. Furthermore, we demonstrate that the acetylated residues in Smad7 also are targeted by ubiquitination and that acetylation of these lysine residues prevents subsequent ubiquitination. Specifically, acetylation of Smad7 protects it against ubiquitination and degradation mediated by the ubiquitin ligase Smurf1. Thus, our data suggest that competition between ubiquitination and acetylation of overlapping lysine residues constitutes a novel mechanism to regulate protein stability.
Summary | Full Text | PDF (564 kb) - …more
Copyright © 2000 Cell Press. All rights reserved.
Molecular Cell, Volume 5, Issue 4, 745-751, 1 April 2000
doi:10.1016/S1097-2765(00)80253-1
Short Article
Acetylation Regulates Transcription Factor Activity at Multiple Levels
Evi Soutoglou1, Nitsa Katrakili1 and Iannis Talianidis1, *, *, 
Corresponding author: Iannis Talianidis, 30 81 39 1173 (phone), 30 81 39 1101 (fax)Summary
CREB-binding protein (CBP) possesses an intrinsic acetyltransferase activity capable of acetylating nucleosomal histones as well as several nonhistone proteins. Here, it is shown that CBP can acetylate hepatocyte nuclear factor-4 (HNF-4), a member of the nuclear hormone receptor family, at lysine residues within the nuclear localization sequence. CBP-mediated acetylation is crucial for the proper nuclear retention of HNF-4, which is otherwise transported out to the cytoplasm via the CRM1 pathway. Acetylation also increases HNF-4 DNA binding activity and its affinity of interaction with CBP itself and is required for target gene activation. The results show that acetylation is a key posttranslational modification that may affect several properties of a transcription factor critical for the execution of its biological functions.
