Oncogenic intra-p53 family member interactions in human cancers
The p53 gene family members p53, p73 and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologues but hold peculiar functional properties. p53, p73 and p63 are tumor suppressor genes that promote differentiation, sen...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-03-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00077/full |
| _version_ | 1811265361117446144 |
|---|---|
| author | Maria eFerraiuolo Silvia eDi Agostino Giovanni eBlandino Sabrina eStrano |
| author_facet | Maria eFerraiuolo Silvia eDi Agostino Giovanni eBlandino Sabrina eStrano |
| author_sort | Maria eFerraiuolo |
| collection | DOAJ |
| description | The p53 gene family members p53, p73 and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologues but hold peculiar functional properties. p53, p73 and p63 are tumor suppressor genes that promote differentiation, senescence and apoptosis. p53, unlike p73 and p63, is frequently mutated in cancer often displaying oncogenic gain of function (GOF) activities correlated with the induction of proliferation, invasion, chemoresistance and genomic instability in cancer cells. These oncogenic functions are promoted either by the aberrant transcriptional cooperation of mutant p53 (mutp53) with transcription cofactors (e.g., NF-Y, E2F1, Vitamin D Receptor (VDR), Ets-1, NF-kB and YAP) or by the interaction with the p53 family members, p73 and p63, determining their functional inactivation. The instauration of these aberrant transcriptional networks leads to increased cell growth, low activation of DNA damage response pathways (DNA damage response (DDR), DNA double-strand breaks (DSBs) response), enhanced invasion and high chemoresistance to different conventional chemotherapeutic treatments. Several studies have clearly shown that different cancers harboring mutant p53 proteins exhibit a poor prognosis when compared to those carrying wild type p53 (wt-p53) protein. The interference of mutantp53/p73 and/or mutantp53/p63 interactions, thereby restoring p53, p73 and p63 tumor suppression functions, could be among the potential therapeutic strategies for the treatment of mutant p53 human cancers. |
| first_indexed | 2024-04-12T20:22:15Z |
| format | Article |
| id | doaj.art-188e7445c2f44af1b7e161970706bb2a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T20:22:15Z |
| publishDate | 2016-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-188e7445c2f44af1b7e161970706bb2a2022-12-22T03:17:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2016-03-01610.3389/fonc.2016.00077191070Oncogenic intra-p53 family member interactions in human cancersMaria eFerraiuolo0Silvia eDi Agostino1Giovanni eBlandino2Sabrina eStrano3Regina Elena National Cancer InstituteRegina Elena National Cancer InstituteRegina Elena National Cancer InstituteRegina Elena National Cancer InstituteThe p53 gene family members p53, p73 and p63 display several isoforms derived from the presence of internal promoters and alternative splicing events. They are structural homologues but hold peculiar functional properties. p53, p73 and p63 are tumor suppressor genes that promote differentiation, senescence and apoptosis. p53, unlike p73 and p63, is frequently mutated in cancer often displaying oncogenic gain of function (GOF) activities correlated with the induction of proliferation, invasion, chemoresistance and genomic instability in cancer cells. These oncogenic functions are promoted either by the aberrant transcriptional cooperation of mutant p53 (mutp53) with transcription cofactors (e.g., NF-Y, E2F1, Vitamin D Receptor (VDR), Ets-1, NF-kB and YAP) or by the interaction with the p53 family members, p73 and p63, determining their functional inactivation. The instauration of these aberrant transcriptional networks leads to increased cell growth, low activation of DNA damage response pathways (DNA damage response (DDR), DNA double-strand breaks (DSBs) response), enhanced invasion and high chemoresistance to different conventional chemotherapeutic treatments. Several studies have clearly shown that different cancers harboring mutant p53 proteins exhibit a poor prognosis when compared to those carrying wild type p53 (wt-p53) protein. The interference of mutantp53/p73 and/or mutantp53/p63 interactions, thereby restoring p53, p73 and p63 tumor suppression functions, could be among the potential therapeutic strategies for the treatment of mutant p53 human cancers.http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00077/fullApoptosishomologyisoformsprotein-protein interactionTarget genesgain of function |
| spellingShingle | Maria eFerraiuolo Silvia eDi Agostino Giovanni eBlandino Sabrina eStrano Oncogenic intra-p53 family member interactions in human cancers Frontiers in Oncology Apoptosis homology isoforms protein-protein interaction Target genes gain of function |
| title | Oncogenic intra-p53 family member interactions in human cancers |
| title_full | Oncogenic intra-p53 family member interactions in human cancers |
| title_fullStr | Oncogenic intra-p53 family member interactions in human cancers |
| title_full_unstemmed | Oncogenic intra-p53 family member interactions in human cancers |
| title_short | Oncogenic intra-p53 family member interactions in human cancers |
| title_sort | oncogenic intra p53 family member interactions in human cancers |
| topic | Apoptosis homology isoforms protein-protein interaction Target genes gain of function |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2016.00077/full |
| work_keys_str_mv | AT mariaeferraiuolo oncogenicintrap53familymemberinteractionsinhumancancers AT silviaediagostino oncogenicintrap53familymemberinteractionsinhumancancers AT giovannieblandino oncogenicintrap53familymemberinteractionsinhumancancers AT sabrinaestrano oncogenicintrap53familymemberinteractionsinhumancancers |