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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

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

K Yukawa, T Tanaka, S Tsuji, S Akira

Brain Res Mol Brain Res. 1999 May 21;69(1):124-34.

PMID: 10350644

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4246382	p300-Ch1 (302-531) human			Price

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