Cargando…
p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality?
Identification of p73 as a structural homolog of p53 fueled early studies aimed at determining if it was capable of performing p53-like functions. This led to a conundrum as p73 was discovered to be hardly mutated in cancers, and yet, TAp73, the full-length form, was found capable of performing p53-...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072922/ https://www.ncbi.nlm.nih.gov/pubmed/32079264 http://dx.doi.org/10.3390/ijms21041346 |
_version_ | 1783506519231299584 |
---|---|
author | Wang, Chao Teo, Cui Rong Sabapathy, Kanaga |
author_facet | Wang, Chao Teo, Cui Rong Sabapathy, Kanaga |
author_sort | Wang, Chao |
collection | PubMed |
description | Identification of p73 as a structural homolog of p53 fueled early studies aimed at determining if it was capable of performing p53-like functions. This led to a conundrum as p73 was discovered to be hardly mutated in cancers, and yet, TAp73, the full-length form, was found capable of performing p53-like functions, including transactivation of many p53 target genes in cancer cell lines. Generation of mice lacking p73/TAp73 revealed a plethora of developmental defects, with very limited spontaneous tumors arising only at a later stage. Concurrently, novel TAp73 target genes involved in cellular growth promotion that are not regulated by p53 were identified, mooting the possibility that TAp73 may have diametrically opposite functions to p53 in tumorigenesis. We have therefore comprehensively evaluated the TAp73 target genes identified and validated in human cancer cell lines, to examine their contextual relevance. Data from focused studies aimed at appraising if p53 targets are also regulated by TAp73—often by TAp73 overexpression in cell lines with non-functional p53—were affirmative. However, genome-wide and phenotype-based studies led to the identification of TAp73-regulated genes involved in cellular survival and thus, tumor promotion. Our analyses therefore suggest that TAp73 may not necessarily be p53’s natural substitute in enforcing tumor suppression. It has likely evolved to perform unique functions in regulating developmental processes and promoting cellular growth through entirely different sets of target genes that are not common to, and cannot be substituted by p53. The p53-related targets initially reported to be regulated by TAp73 may therefore represent an experimental possibility rather than the reality. |
format | Online Article Text |
id | pubmed-7072922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70729222020-03-19 p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? Wang, Chao Teo, Cui Rong Sabapathy, Kanaga Int J Mol Sci Review Identification of p73 as a structural homolog of p53 fueled early studies aimed at determining if it was capable of performing p53-like functions. This led to a conundrum as p73 was discovered to be hardly mutated in cancers, and yet, TAp73, the full-length form, was found capable of performing p53-like functions, including transactivation of many p53 target genes in cancer cell lines. Generation of mice lacking p73/TAp73 revealed a plethora of developmental defects, with very limited spontaneous tumors arising only at a later stage. Concurrently, novel TAp73 target genes involved in cellular growth promotion that are not regulated by p53 were identified, mooting the possibility that TAp73 may have diametrically opposite functions to p53 in tumorigenesis. We have therefore comprehensively evaluated the TAp73 target genes identified and validated in human cancer cell lines, to examine their contextual relevance. Data from focused studies aimed at appraising if p53 targets are also regulated by TAp73—often by TAp73 overexpression in cell lines with non-functional p53—were affirmative. However, genome-wide and phenotype-based studies led to the identification of TAp73-regulated genes involved in cellular survival and thus, tumor promotion. Our analyses therefore suggest that TAp73 may not necessarily be p53’s natural substitute in enforcing tumor suppression. It has likely evolved to perform unique functions in regulating developmental processes and promoting cellular growth through entirely different sets of target genes that are not common to, and cannot be substituted by p53. The p53-related targets initially reported to be regulated by TAp73 may therefore represent an experimental possibility rather than the reality. MDPI 2020-02-17 /pmc/articles/PMC7072922/ /pubmed/32079264 http://dx.doi.org/10.3390/ijms21041346 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Wang, Chao Teo, Cui Rong Sabapathy, Kanaga p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title | p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title_full | p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title_fullStr | p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title_full_unstemmed | p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title_short | p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? |
title_sort | p53-related transcription targets of tap73 in cancer cells—bona fide or distorted reality? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072922/ https://www.ncbi.nlm.nih.gov/pubmed/32079264 http://dx.doi.org/10.3390/ijms21041346 |
work_keys_str_mv | AT wangchao p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality AT teocuirong p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality AT sabapathykanaga p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality |