Regulation of transcription factor C/ATF by the cAMP signal activation in hippocampal neurons, and molecular interaction of C/ATF with signal integrator CBP/p300.
The CCAAT/enhancer binding proteins related activating transcription factor, C/ATF, is a mouse leucine-zipper transcription factor which is structurally homologous to ApCREB2, a suppressor integral to long-term synaptic plasticity in Aplysia. To gain a clue to whether C/ATF is involved in long-term plasticities of brain, we examined if the expression levels ... of C/ATF are modulated by cAMP, an inducer crucial for memory formation in Aplysia, Drosophila and mice. Our in situ hybridization analysis revealed the expression of C/ATF mRNA in hippocampal neurons. C/ATF protein levels increased after the cAMP signal stimulation in hippocampal neurons, while C/ATF mRNA levels remained constant. The human activating transcription factor 4 (hATF4), another homolog of ApCREB2, interacts with multiple domains of the coactivator CREB-binding protein (CBP), resulting in the potentiation of its ability to activate transcription. As expected, C/ATF was found to interact with three domains of CBP including CREB binding domain or kinase-inducible interaction (KIX) domain, the third cysteine-histidine-rich region (CH3 domain) and the nuclear receptor coactivator p160/SRC-1-interacting domain. Interestingly, C/ATF was further found to interact strongly with CREB binding protein/p300 (CBP/p300) CH1 domain. Mammalian two hybrid assays indicated that the interaction between C/ATF and CBP/p300 can occur in mammalian cells, and that the p300 CH1 domain is critical for the interaction. Thus, C/ATF may be implicated in transcription-dependent phase of hippocampal long-term plasticities through the modulation of its protein level under cAMP signal and the interaction with signal integrator, CBP/p300.
Mesh Terms:
Activating Transcription Factor 4, Animals, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, Cyclic AMP, Cyclic AMP Response Element-Binding Protein, DNA Probes, DNA-Binding Proteins, E1A-Associated p300 Protein, Gene Expression, Hippocampus, Leucine Zippers, Mice, Neurons, Nuclear Proteins, Protein Binding, Rats, Recombinant Fusion Proteins, STAT2 Transcription Factor, Signal Transduction, Trans-Activators, Transcription Factors
Activating Transcription Factor 4, Animals, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, Cyclic AMP, Cyclic AMP Response Element-Binding Protein, DNA Probes, DNA-Binding Proteins, E1A-Associated p300 Protein, Gene Expression, Hippocampus, Leucine Zippers, Mice, Neurons, Nuclear Proteins, Protein Binding, Rats, Recombinant Fusion Proteins, STAT2 Transcription Factor, Signal Transduction, Trans-Activators, Transcription Factors
Brain Res. Mol. Brain Res.
Date: May. 21, 1999
PubMed ID: 10350644
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