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CAMP-responsive element-binding protein (CREB) and cAMP co-regulate activator protein 1 (AP1) -dependent regeneration-associated gene expression and neurite growth

Ma, T.C.; Barco, A.; Ratan, R.R.; Willis, D.E.

Journal of Biological Chemistry 289(47): 32914-32925

2014


ISSN/ISBN: 1083-351X
PMID: 25296755
DOI: 10.1074/jbc.m114.582460
Accession: 056982309

To regenerate damaged axons, neurons must express a cassette of regeneration-associated genes (RAGs) that increases intrinsic growth capacity and confers resistance to extrinsic inhibitory cues. Here we show that dibutyrl-cAMP or forskolin combined with constitutive-active CREB are superior to either agent alone in driving neurite growth on permissive and inhibitory substrates. Of the RAGs examined, only arginase 1 (Arg1) expression correlated with the increased neurite growth induced by the cAMP/CREB combination, both of which were AP1-dependent. This suggests that cAMP-induced AP1 activity is necessary and interacts with CREB to drive expression of RAGs relevant for regeneration and demonstrates that combining a small molecule (cAMP) with an activated transcription factor (CREB) stimulates the gene expression necessary to enhance axonal regeneration.

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