RGD Reference Report - A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. - Rat Genome Database

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

Authors: Tedeschi, A  Nguyen, T  Puttagunta, R  Gaub, P  Di Giovanni, S 
Citation: Tedeschi A, etal., Cell Death Differ. 2009 Apr;16(4):543-54. Epub 2008 Dec 5.
RGD ID: 2311715
Pubmed: PMID:19057620   (View Abstract at PubMed)
DOI: DOI:10.1038/cdd.2008.175   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of DNA binding  IMP 2311715 RGD 
positive regulation of DNA-binding transcription factor activity  IMP 2311715 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cis-regulatory region sequence-specific DNA binding  IDA 2311715 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)


Additional Information