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 <i>p73</i> was discovered to be hardly mutated in cancers, and yet, TAp73, the full-length form, was found capable...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/4/1346 |
| _version_ | 1811193016411488256 |
|---|---|
| author | Chao Wang Cui Rong Teo Kanaga Sabapathy |
| author_facet | Chao Wang Cui Rong Teo Kanaga Sabapathy |
| author_sort | Chao Wang |
| collection | DOAJ |
| 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 <i>p73</i> 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. |
| first_indexed | 2024-04-12T00:01:20Z |
| format | Article |
| id | doaj.art-1495d26ba11348afb336384f1e7098d5 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T00:01:20Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1495d26ba11348afb336384f1e7098d52022-12-22T03:56:14ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01214134610.3390/ijms21041346ijms21041346p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality?Chao Wang0Cui Rong Teo1Kanaga Sabapathy2Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, SingaporeCancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, SingaporeDivision of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore 169610, SingaporeIdentification 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 <i>p73</i> 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.https://www.mdpi.com/1422-0067/21/4/1346cancer cell linesp53tap73transcriptional targetstumor suppression |
| spellingShingle | Chao Wang Cui Rong Teo Kanaga Sabapathy p53-Related Transcription Targets of TAp73 in Cancer Cells—Bona Fide or Distorted Reality? International Journal of Molecular Sciences cancer cell lines p53 tap73 transcriptional targets tumor suppression |
| 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 | cancer cell lines p53 tap73 transcriptional targets tumor suppression |
| url | https://www.mdpi.com/1422-0067/21/4/1346 |
| work_keys_str_mv | AT chaowang p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality AT cuirongteo p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality AT kanagasabapathy p53relatedtranscriptiontargetsoftap73incancercellsbonafideordistortedreality |