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Updated: Jul 4, 2026
09:20
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Attenuation of a phosphorylation-dependent activator by an HDAC-PP1 complex
Gianluca Canettieri1, Ianessa Morantte, Ernesto Guzmán
1Peptide Biology Laboratories, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Structural Biology
|February 5, 2003
Summary
Histone deacetylase 1 (HDAC1) represses transcription by blocking cAMP-responsive element-binding protein (CREB) phosphorylation. HDAC1 interacts with protein phosphatase 1 (PP1) to maintain CREB in its inactive, unphosphorylated state.
Area of Science:
- Molecular Biology
- Epigenetics
- Signal Transduction
Background:
- Cyclic AMP (cAMP) regulates transcription via CREB phosphorylation at Ser133.
- Phosphorylation enables recruitment of co-activators like CBP/P300, leading to histone acetylation and gene activation.
- Histone deacetylase (HDAC) inhibitors suggest HDACs may negatively regulate CREB activity.
Purpose of the Study:
- To investigate the role of HDACs in regulating CREB activity.
- To elucidate the mechanism by which HDACs might repress CREB-mediated transcription.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Co-purification studies to confirm protein complexes.
- Analysis of CREB phosphorylation status in response to cAMP stimulation.
Main Results:
- HDAC1 associates with CREB and inhibits its Ser133 phosphorylation.
- HDAC1 forms a stable complex with protein phosphatase 1 (PP1).
- This interaction facilitates PP1-mediated dephosphorylation of CREB, particularly during pre-stimulus and attenuation phases.
Conclusions:
- HDAC1 acts as a repressor of CREB activity by promoting its dephosphorylation.
- HDAC1 coordinates signaling pathways with chromatin modification to control gene transcription.
- This reveals a novel mechanism for regulating phosphorylation-dependent transcription factors.
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