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Publication : A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration.

First Author  Tedeschi A Year  2009
Journal  Cell Death Differ Volume  16
Issue  4 Pages  543-54
PubMed ID  19057620 Mgi Jnum  J:158081
Mgi Id  MGI:4437994 Doi  10.1038/cdd.2008.175
Citation  Tedeschi A, et al. (2009) A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. Cell Death Differ 16(4):543-54
abstractText  Transcription regulates axon outgrowth and regeneration. However, to date, no transcription complexes have been shown to control axon outgrowth and regeneration by regulating axon growth genes. Here, we report that the tumor suppressor p53 and its acetyltransferases CBP/p300 form a transcriptional complex that regulates the axonal growth-associated protein 43, a well-characterized pro-axon outgrowth and regeneration protein. Acetylated p53 at K372-3-82 drives axon outgrowth, GAP-43 expression, and binds specific elements on the neuronal GAP-43 promoter in a chromatin environment through CBP/p300 signaling. Importantly, in an axon regeneration model, both CBP and p53 K372-3-82 are induced following axotomy in facial motor neurons, where p53 K372-3-82 occupancy of GAP-43 promoter is enhanced as shown by in vivo chromatin immunoprecipitation. Finally, by comparing wild-type and p53 null mice, we demonstrate that the p53/GAP-43 transcriptional module is specifically switched on during axon regeneration in vivo. These data contribute to the understanding of gene regulation in axon outgrowth and may suggest new molecular targets for axon regeneration.
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