The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2
The transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 promotes cell proliferation by activating growth-promoting genes upon growth stimulation. In contrast, E2F1 contributes to tumor suppression by activating tumor suppressor genes, such as <i>ARF</i>, u...
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2024-10-01
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| author | Lin Zhao Rinka Nakajima Yaxuan Zhou Mashiro Shirasawa Mariana Fikriyanti Yuki Kamiya Hiroyuki Toh Hideyuki Komori Ritsuko Iwanaga Andrew P. Bradford Hideo Nishitani Kenta Kurayoshi Keigo Araki Kiyoshi Ohtani |
| author_facet | Lin Zhao Rinka Nakajima Yaxuan Zhou Mashiro Shirasawa Mariana Fikriyanti Yuki Kamiya Hiroyuki Toh Hideyuki Komori Ritsuko Iwanaga Andrew P. Bradford Hideo Nishitani Kenta Kurayoshi Keigo Araki Kiyoshi Ohtani |
| author_sort | Lin Zhao |
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| description | The transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 promotes cell proliferation by activating growth-promoting genes upon growth stimulation. In contrast, E2F1 contributes to tumor suppression by activating tumor suppressor genes, such as <i>ARF</i>, upon loss of pRB function, a major oncogenic change. The transactivation domain of E2F1 has previously been mapped to the C-terminal region. We show here that the N-terminal region of E2F1 is critical for the activation of tumor suppressor genes. Deletion of the N-terminal region dramatically compromised E2F1 activation of tumor suppressor genes. The N-terminal region showed transactivation ability when fused to the DNA-binding domain of GAL4. A search for novel interacting factors with the N-terminal region, using a yeast two-hybrid system, identified the general transcription factor GTF2H2. Overexpression of GTF2H2 enhanced E2F1 activation of tumor suppressor genes and induction of cell death. Conversely, the knockdown of GTF2H2 compromised both. E2F1 binding enhanced the binding of GTF2H2 to target promoters depending on the integrity of the N-terminal region. Taken together, these results suggest that the N-terminal region of E2F1 contains a novel transactivation domain that mediates the activation of tumor suppressor genes, at least in part, by recruiting GTF2H2. |
| format | Article |
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| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-a342bd13182649b890625fdf3eb076182025-08-20T02:08:12ZengMDPI AGBiomolecules2218-273X2024-10-011411135710.3390/biom14111357The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2Lin Zhao0Rinka Nakajima1Yaxuan Zhou2Mashiro Shirasawa3Mariana Fikriyanti4Yuki Kamiya5Hiroyuki Toh6Hideyuki Komori7Ritsuko Iwanaga8Andrew P. Bradford9Hideo Nishitani10Kenta Kurayoshi11Keigo Araki12Kiyoshi Ohtani13Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USADepartment of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USADepartment of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USAGraduate School of Life Science, University of Hyogo, Kamigori, Ako-gun 678-1297, Hyogo, JapanDivision of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, JapanDepartment of Morphological Biology, Ohu University School of Dentistry, 31-1 Misumido Tomitamachi, Koriyama 963-8611, Fukushima, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, JapanThe transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 promotes cell proliferation by activating growth-promoting genes upon growth stimulation. In contrast, E2F1 contributes to tumor suppression by activating tumor suppressor genes, such as <i>ARF</i>, upon loss of pRB function, a major oncogenic change. The transactivation domain of E2F1 has previously been mapped to the C-terminal region. We show here that the N-terminal region of E2F1 is critical for the activation of tumor suppressor genes. Deletion of the N-terminal region dramatically compromised E2F1 activation of tumor suppressor genes. The N-terminal region showed transactivation ability when fused to the DNA-binding domain of GAL4. A search for novel interacting factors with the N-terminal region, using a yeast two-hybrid system, identified the general transcription factor GTF2H2. Overexpression of GTF2H2 enhanced E2F1 activation of tumor suppressor genes and induction of cell death. Conversely, the knockdown of GTF2H2 compromised both. E2F1 binding enhanced the binding of GTF2H2 to target promoters depending on the integrity of the N-terminal region. Taken together, these results suggest that the N-terminal region of E2F1 contains a novel transactivation domain that mediates the activation of tumor suppressor genes, at least in part, by recruiting GTF2H2.https://www.mdpi.com/2218-273X/14/11/1357E2F1pRBARFp53transactivation domainGTF2H2 |
| spellingShingle | Lin Zhao Rinka Nakajima Yaxuan Zhou Mashiro Shirasawa Mariana Fikriyanti Yuki Kamiya Hiroyuki Toh Hideyuki Komori Ritsuko Iwanaga Andrew P. Bradford Hideo Nishitani Kenta Kurayoshi Keigo Araki Kiyoshi Ohtani The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 Biomolecules E2F1 pRB ARF p53 transactivation domain GTF2H2 |
| title | The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 |
| title_full | The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 |
| title_fullStr | The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 |
| title_full_unstemmed | The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 |
| title_short | The N-Terminal Region of the Transcription Factor E2F1 Contains a Novel Transactivation Domain and Recruits General Transcription Factor GTF2H2 |
| title_sort | n terminal region of the transcription factor e2f1 contains a novel transactivation domain and recruits general transcription factor gtf2h2 |
| topic | E2F1 pRB ARF p53 transactivation domain GTF2H2 |
| url | https://www.mdpi.com/2218-273X/14/11/1357 |
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