Post-translational modifications regulate p73 functions
2005
TP53 is a tumor suppressor gene whose product is involved in
cellular growth inhibition, apoptosis and senescence. Two new
classes of proteins recently discovered, p63 and p73 proteins, share
with p53 a high structural homology and overlapping yet specific
functions.
p63 and p73 can be expressed as TA forms that have the
Transcriptional Activation Domain, behave as p53-like proteins and
show variability at the C-terminus due to alternative splicing. Indeed
p63 and p73 can be also expressed from an alternative promoter or
by N-terminal alternative splicing and the products are ΔNp73 or
ΔTAp73 forms that are truncated at the N-teminus and act as
dominant negative proteins of the other p53 family members.
Although p53 family proteins share the main functional domains
and activate the transcription of a subset of common genes, unlike
p53, p73 and p63 do not have clear features of tumor suppressors.
Actually their activity is more complex and still not well defined. The
entire p73 network of proteins, in fact, is involved in neuronal
differentiation, in the apoptotic response to damaging agents
(cisplatin, IR, doxorubicin) and in tumorigenesis.
TP73 gene is transcriptionally regulated by E2F1, in the G1/S
transition and in the DNA damage or oncogenes activated apoptotic
response. The p73 protein functions are modulated by posttranslational
modifications and protein-protein interactions in different
physiopathological cellular contexts.
The aim of this PhD thesis has been the characterization of posttranslational
modifications that regulate p73 transcriptional functions
upon DNA damage and in physiological contexts.
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