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p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Dec 16; Vol. 280 (50), pp. 41537-45. Date of Electronic Publication: 2005 Oct 11. - Publication Year :
- 2005
-
Abstract
- ATF4 plays a crucial role in the cellular response to stress and multiple stress responses pathways converge to the translational up-regulation of ATF4. ATF4 is a substrate of the SCF(betaTrCP) ubiquitin ligase that binds to betaTrCP through phosphorylation on a DSGXXXS motif. We show here that ATF4 stability is also modulated by the histone acetyltransferase p300, which induces ATF4 stabilization by inhibiting its ubiquitination. Despite p300 acetylates ATF4, we found that p300-mediated ATF4 stabilization is independent of p300 catalytic activity, using either the inactive form of p300 or the acetylation mutant ATF4-K311R. ATF4 deleted of its p300 binding domain is no more stabilized by p300 nor recruited into nuclear speckles. In consequence of ATF4 stabilization, both p300 and the catalytically inactive enzyme increase ATF4 transcriptional activity.
- Subjects :
- Amino Acid Motifs
Blotting, Western
CREB-Binding Protein chemistry
Catalysis
Cell Line
Cell Nucleus metabolism
Electrophoresis, Polyacrylamide Gel
Gene Silencing
Genetic Vectors
Glutathione Transferase metabolism
HeLa Cells
Histone Acetyltransferases chemistry
Humans
Immunoprecipitation
Microscopy, Fluorescence
Mutation
Phosphorylation
Plasmids metabolism
Protein Binding
Protein Structure, Tertiary
RNA, Small Interfering metabolism
Transfection
Ubiquitin chemistry
Ubiquitin metabolism
p300-CBP Transcription Factors metabolism
Activating Transcription Factor 4 chemistry
CREB-Binding Protein physiology
Transcription, Genetic
p300-CBP Transcription Factors chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 50
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16219772
- Full Text :
- https://doi.org/10.1074/jbc.M505294200