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the promoter of GAP-43 (
Floriddia, Nguyen, & Di Giovanni, 2011
),
indicating that p53 acetylation may be a crucial event during axonal
regeneration.
In the model of CNS axonal injury where the axons fail to regenerate
spontaneously, as for instance after the optic nerve crush (ONC), the expres-
sion of acetylated p53 at K373 is decreased (
Gaub et al., 2011
). However,
p300 viral overexpression in RGCs at the time of ONC leads to an increase
in p53 acetylation, promoting axonal regeneration likely by driving the
expression of regeneration-associated genes such as GAP-43, Coronin 1b,
and Sprr1a (
Gaub et al., 2011
).
Besides affecting p53 activity and affinity for different set of promoters,
PTMs affect also p53 localization. Indeed, while the acetylated form of p53
seems expressed both in neuronal nuclei and in axons, high levels of phos-
phorylated p53 are expressed at the growth cone in association with the ax-
onal microtubule associated protein tau,
in cultured cortical
and
hippocampal neurons (
Qin et al., 2009
).
Although the role of selected p53 PTMs has been studied in affecting p53
function in neurite outgrowth and axonal regeneration, little is known so far
about the influence of p53 PTMs in the regulation of neurogenesis. How-
ever, recently, JMJD3 and H3K27me3 histone demethylases have been
shown to influence the regulation of neurogenesis and in particular of pro-
genitor cell fate specification. Interestingly, during neural stem cell matura-
tion, JMJD3 stabilizes the level of p53 through ARF activity, causing its
nuclear translocation (
Sola et al., 2011
), suggesting that p53 and JMJD3
interaction is important for neural stem cell differentiation.
All together, these evidences corroborate the concept that PTMs confer
dynamic and distinct regulatory functions to p53. It would be therefore
interesting to determine by an unbiased approach the pattern of p53 PTMs
that occurs during neural stem cell development and maturation in order to
elucidate the p53-dependent decision, making process between neural stem
cells quiescence, proliferation, differentiation, and death.
5. CONCLUSIONS AND PERSPECTIVES
During neuronal development, new neurons are generated, as a result
of a finely tuned and dynamic balance among cellular quiescence, prolifer-
ation, survival, and differentiation. Indeed, for normal tissue growth to oc-
cur, all these processes have to be tightly controlled and coordinated. Here,
we have discussed evidence that supports an important role for the tumor
