Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay
P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribut...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/2/277 |
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| author | Paola Monti Vaclav Brazda Natália Bohálová Otília Porubiaková Paola Menichini Andrea Speciale Renata Bocciardi Alberto Inga Gilberto Fronza |
| author_facet | Paola Monti Vaclav Brazda Natália Bohálová Otília Porubiaková Paola Menichini Andrea Speciale Renata Bocciardi Alberto Inga Gilberto Fronza |
| author_sort | Paola Monti |
| collection | DOAJ |
| description | P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic <i>PUMA</i> target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites. |
| first_indexed | 2024-03-09T00:52:02Z |
| format | Article |
| id | doaj.art-f4fb1b4d1fd44c8fb67dca8c8da3abe3 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T00:52:02Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f4fb1b4d1fd44c8fb67dca8c8da3abe32023-12-11T17:10:18ZengMDPI AGGenes2073-44252021-02-0112227710.3390/genes12020277Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional AssayPaola Monti0Vaclav Brazda1Natália Bohálová2Otília Porubiaková3Paola Menichini4Andrea Speciale5Renata Bocciardi6Alberto Inga7Gilberto Fronza8Mutagenesis and Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyInstitute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicInstitute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 61265 Brno, Czech RepublicMutagenesis and Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyMutagenesis and Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Largo P. Daneo 3, 16132 Genoa, ItalyLaboratory of Transcriptional Networks, Department of Cellular, Computational and Integrative Biology, CIBIO, University of Trento, via Sommarive 9, 38123 Trento, ItalyMutagenesis and Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyP53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic <i>PUMA</i> target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites.https://www.mdpi.com/2073-4425/12/2/277P53 familyyeastG-quadruplex (G4) prone sequencewild-type and mutant P53/P63 proteinstransactivation potential |
| spellingShingle | Paola Monti Vaclav Brazda Natália Bohálová Otília Porubiaková Paola Menichini Andrea Speciale Renata Bocciardi Alberto Inga Gilberto Fronza Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay Genes P53 family yeast G-quadruplex (G4) prone sequence wild-type and mutant P53/P63 proteins transactivation potential |
| title | Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay |
| title_full | Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay |
| title_fullStr | Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay |
| title_full_unstemmed | Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay |
| title_short | Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay |
| title_sort | evaluating the influence of a g quadruplex prone sequence on the transactivation potential by wild type and or mutant p53 family proteins through a yeast based functional assay |
| topic | P53 family yeast G-quadruplex (G4) prone sequence wild-type and mutant P53/P63 proteins transactivation potential |
| url | https://www.mdpi.com/2073-4425/12/2/277 |
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