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.

Merlo, P. (2005). Post-translational modifications regulate p73 functions.

Post-translational modifications regulate p73 functions

MERLO, PAOLA
2005-12-20

Abstract

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.
A.A. 2004/2005
Biochimica e biologia molecolare
16.
Settore BIO/12
English
Tesi di dottorato
Merlo, P. (2005). Post-translational modifications regulate p73 functions.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/188
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